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|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F15292170%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F15292170%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 15292170 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 15292170"/>
|
||
<input type="hidden" name="email-subject-hash" value="7f5d04745601d6e4312fd93a444378e39f61aeaa337ae4bbb6a1d42efae85d68"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="15292170">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)77085-7"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=15292170&db=pubmed&nlmid=2985121R"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="15292170"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/15292170/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=15292170&db=pubmed&nlmid=2985121R"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="15292170"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/15292170/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/15292170/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="15292170" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F15292170%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="8MXMUNMmKEo8ZaRr6yBCNGF8nPRXdORaXkXZydiEpG3UkevxXV1zZEakUjWjk2ni"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2004 Oct 8;279(41):43296-306.</span>
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<h1 class="heading-title">
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Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase
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Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase
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Methylation of Lys79 on histone H3 by Dot1p is important for gene silencing. The elongated structure of the conserved core of yeast Dot1p contains an N-terminal helical domain and a seven-stranded catalytic domain that harbors the binding site for the methyl-donor and an active site pocket sided with conserved hydrophobic residues. The S-adenosyl-L-homocysteine exhibits an extended conformation distinct from the folded conformation observed in structures of SET domain histone lysine methyltransferases. A catalytic asparagine (Asn479), located at the bottom of the active site pocket, suggests a mechanism similar to that employed for amino methylation in DNA and protein glutamine methylation. The acidic, concave cleft between the two domains contains two basic residue binding pockets that could accommodate the outwardly protruding basic side chains around Lys79 of histone H3 on the disk-like nucleosome surface. Biochemical studies suggest that recombinant Dot1 proteins are active on recombinant nucleosomes, free of any modifications.
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<p> Fig. 1. Conserved Dot1-core region </p>
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Fig. 1. Conserved Dot1-core region
|
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<div class="figure-caption-contents"><i>A</i>, schematic representation of Dot1 homologues from yeast and human. A proteolytic cleavage site of the yeast Dot1 is labeled <i>V8. B</i>, sequence alignment of the conserved Dot1 core region. The alignment includes members of the Dot1 family from various species: <i>S. cerevisiae</i> (NP_010728), <i>C. elegans</i> (NM_058569), <i>Drosophila</i> (AE003675), <i>A. gambiae</i> (EAA03558), mouse (BB678539), and human (NP_115871). The residue number and secondary structural elements of yeast Dot1 (helices A-M and strands 1–11) are shown <i>above</i> the aligned sequences. <i>Dashed lines</i> indicate disordered regions. The amino acids highlighted are invariant (<i>white letter against black background</i>) and conserved (<i>black against gray</i>) among six members of the Dot1 family. The <i>letters above</i> the sequences indicate the structural/functional roles of the corresponding yeast Dot1 residues: <i>h</i> indicates intramolecular hydrophobic interaction, <i>i</i> indicates intramolecular nonhydrophobic (polar or charge) interaction, <i>s</i> indicates surface-exposed invariant residues potentially important for substrate binding, <i>t</i> indicates structural residue Gly involved in the sharp turn, <i>asterisk</i> indicates cofactor-interacting residue, <i>K</i> indicates residues forming the target Lys binding pocket, and <i>R</i> indicates residues potentially involved in binding an Arg (most likely from the substrate). The conserved sequence motifs characteristic of class I MTases are labeled with <i>roman numbers</i> according to Ref. .</div>
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<p> Fig. 2. Activity of yeast Dot1p </p>
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<div class="figure-caption-contents"><i> A… </i></div>
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<p> Fig. 2. Activity of yeast Dot1p </p>
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<div class="figure-caption-contents"><i> A </i> , enzymatic activity of purified Dot1p proteins, measured…</div>
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Fig. 2. Activity of yeast Dot1p
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<div class="figure-caption-contents"><i>A</i>, enzymatic activity of purified Dot1p proteins, measured as trichloroacetic acid-precipitable counts. The enzymes used were all purified recombinant proteins. The substrate nucleosomes were either purified from chicken erythrocyte (<i>left panel</i>) or recombinant nucleosome (<i>right panel</i>). Protein-arginine MTase (PRMT1), used as positive control, was active on both recombinant nucleosomes and histones. <i>B</i>, fluorographic results of an AdoMet cross-linking experiment at pH 8.5 (<i>right panel</i>) are shown with results of Coomassie staining to control for the amount of deletion mutant proteins tested (<i>left panel</i>). <i>C</i>, binding of mononucleosome (from chicken erythrocyte, <i>top panel</i>) and DNA (36-base pair, <i>bottom panel</i>) by yeast Dot1p, two deletion mutants (Δ157 and Δ172), and Δ157 point mutants (E422D or A, W543F or A, and Y550F or A) were analyzed by gel shift assays at three different protein:nucleosome or protein:DNA ratios. <i>D</i>, Dot1p methyl transfer activity is stimulated by preincubation of a 150-base pair DNA with enzyme. <i>Top panel</i>, trichloroacetic acid-precipitable counts. <i>Bottom panel</i>, autoradiograph (the enzyme:DNA ratio of 1:5). <i>E</i>, HKMT activities of Dot1p and deletion mutant Δ157 as a function of pH (<i>top panel</i>) and AdoMet cross-linking as a function of pH (<i>bottom panel</i>). <i>F</i>, Tyr<sup>550</sup> adopts a different rotamer conformation as Tyr<sup>312</sup> in human Dot1L. <i>G</i>, biochemical properties of Δ157 point mutations: <i>top</i>, HKMT activity using mononucleosome substrate; <i>middle</i>, AdoMet binding analyzed by cross-linking experiments showing Coomassie stain and fluorography; <i>bottom</i>, DNA binding analyzed by gel shift assay at three protein:DNA ratios. All mutant proteins were expressed at levels similar to that of the Δ157 wild-type.</div>
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<strong class="figure-label">
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<p> Fig. 3. Structure of yeast Dot1p </p>
|
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<div class="figure-caption-contents"><i> A… </i></div>
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<strong class="figure-label">
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<p> Fig. 3. Structure of yeast Dot1p </p>
|
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<div class="figure-caption-contents"><i> A </i> , a trimer of Δ157 formed in the…</div>
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Fig. 3. Structure of yeast Dot1p
|
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<div class="figure-caption-contents"><i>A</i>, a trimer of Δ157 formed in the crystallographic asymmetric unit. The trimer interface is formed between the N-terminal helix <i>α</i>A (which is unique to yeast Dot1p and <i>C. elegans</i> homologue, see Fig. 1<i>B</i>) and the outer surface of the AdoHcy-binding site of a neighboring non-crystallographic related molecule. We also note that yeast Hst2, a member of Sir2 family of NAD<sup>+</sup>-dependent protein deacetylases, forms a functional homotrimer mediated by the N-terminal extension to the central catalytic core domain (62), which is characteristic of the other Sir2 homologues. On the other hand, helix <i>α</i>A may be involved in regulation of Dot1p via protein-protein interactions. <i>B</i>, monomer structure of Δ157. The N-terminal clamp is shown in <i>purple</i>, the N-terminal helical domain in <i>green</i>, and the C-terminal catalytic domain in <i>orange</i>. The bound AdoHcy is shown as a <i>stick model. C</i>, the polar interface between the N- and C-terminal domains. <i>D</i>, a GRASP (63) representation showing the cleft between the two domains and a surface hole, through which the adenine ring of AdoHcy is visible. <i>E</i>, a GRASP representation, 90° rotated from the view in <i>panel D</i>, showing the conserved motifs (X, IV, and VIII) surrounding the active site pocket, through which the AdoHcy sulfur atom is visible. Conserved motifs I, II, and III are buried and invisible from the surface. In addition, there are three surface-exposed invariant residues, Tyr<sup>364</sup> and Phe<sup>367</sup> in the loop after helix <i>α</i>G, and Lys<sup>508</sup> after strand <i>β</i>9 (Fig. 1<i>B</i>). The surface locations of Tyr<sup>364</sup> and Phe<sup>367</sup>, approximate to the motif X that provides residues in the active site formation (Val<sup>371</sup> and Gly<sup>373</sup>, Fig. 4<i>B</i>), the Arg-binding site (Tyr<sup>372</sup> and Glu<sup>374</sup>, Fig. 4<i>C</i>), and the lid to the AdoHcy binding site (Fig. 5, <i>C</i> and <i>E</i>), suggests these two conserved residues may have implications in specific enzyme-substrate interactions. Lys<sup>508</sup>, located right next to Phe<sup>481</sup> of motif IV, might also contribute to substrate binding and/or catalysis. <i>F</i>, a model of Dot1p docked with a nucleosome. The structure of the nucleosome core particle is shown as ribbons (<i>red</i>, H3; <i>green</i>, H4; <i>magenta</i>, H2A; <i>yellow</i>, H2B; <i>gray lines</i>, DNA). The model was put together by aligning the target Lys<sup>79</sup> of histone H3, located on the nucleosome disk surface, with the active site pocket of Dot1p. By rotating the Dot1p along the Lys<sup>79</sup> active site alignment, the N-terminal residues, either disordered (residues 158–175) or not included in the crystallization (residues 1–157), could be in a position to contact DNA directly and/or involved in interaction with monoubiquitin covalently attached to histone H2B Lys<sup>123</sup>. In the model shown, no conformational changes are required to dock. However, major conformational changes of either the nucleosome and/or the enzyme would be needed to allow the side chain of Lys<sup>79</sup> of H3 moving additional a few angstroms into the active site pocket.</div>
|
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|
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|
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<p> Fig. 4. Putative substrate binding cleft </p>
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<p> Fig. 4. Putative substrate binding cleft </p>
|
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<div class="figure-caption-contents"><i> A </i> , the surface charge distribution is displayed as…</div>
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Fig. 4. Putative substrate binding cleft
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<div class="figure-caption-contents"><i>A</i>, the surface charge distribution is displayed as <i>blue</i> for positive, <i>red</i> for negative, and <i>white</i> for neutral. The bound AdoHcy sulfur atom can be seen through the active site pocket. <i>B</i>, five hydrophobic residues form the active site pocket (the corresponding residue from human Dot1L is in <i>parentheses</i>). The opening of the pocket is ∼4 × 5 Å, where the target Lys could be inserted. <i>C</i>, a difference electron density map (contoured at 1.5<i>σ</i>) indicates that an Arg residue can be fit into a surface-binding pocket formed partly by invariant residues of motif X (Glu<sup>374</sup> and Tyr<sup>372</sup>) and Tyr<sup>350</sup> of helix <i>α</i>F. <i>D</i>, a difference electron density (contoured at 1.2<i>σ</i>) can be fit by a stretch of peptide, possibly from the C terminus of a crystallographically related molecule. The identity of the side chain cannot be determined unambiguously, except a Lys residue bound in a surface pocket with interaction to Asp<sup>301</sup>. The main chain atoms of the Lys residue form <i>β</i>-strand like interactions with the N-terminal residue Thr<sup>178</sup>. <i>E</i>, the basic nucleosomal disk surface around Lys<sup>79</sup> (<i>green</i>) of histone H3 contains many positively charged residues (<i>blue</i>). <i>F</i>, biochemical properties of Δ157 point mutations in the Arg and Lys binding pockets: <i>top</i>, HKMT activity using mononucleosome (from chicken erythrocyte) as substrates; <i>middle</i>, AdoMet binding analyzed by cross-linking experiments showing Coomassie stain and fluorography; <i>bottom</i>, DNA binding and mononucleosome binding analyzed by gel shift assay at three protein:DNA or protein:nucleosome ratios. All mutant proteins were expressed at levels similar to that of the Δ157 wild-type.</div>
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<p> Fig. 5. AdoHcy binding site and active… </p>
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<p> Fig. 5. AdoHcy binding site and active site </p>
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<div class="figure-caption-contents"><i> A </i> , superimposition of AdoHcy conformations in…</div>
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Fig. 5. AdoHcy binding site and active site
|
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<div class="figure-caption-contents"><i>A</i>, superimposition of AdoHcy conformations in yeast Dot1p and SET domain HKMT DIM-5 (19). <i>B</i>, stereo view of the AdoHcy binding site. The difference electron density map is contoured at 2.5<i>σ. Dashed lines</i> indicate hydrogen bonds. The letter <i>w</i> indicates bound water molecules. Interactions involving main chain (<i>mc</i>) atoms are indicated in <i>parentheses. C</i>, stereo view of active site. The AdoHcy is in van der Waals surface model, colored with <i>red</i> for oxygen atoms, <i>blue</i> for nitrogen atoms, white for carbon atoms, and <i>green</i> for the sulfur (placed where the transferable methyl group would be attached in AdoMet). <i>D</i>, superimposition of yeast Dot1p (AdoHcy and Asn<sup>479</sup>) and protein glutamine MTase HemK (48) (AdoMet, Asn<sup>197</sup>, and free glutamine). <i>E</i>, structural comparison of yeast Dot1p (residues 176–567; <i>top panel</i>) and human Dot1L (residues 5–332; <i>middle panel</i>). Besides deletion or insertion (located in N and C termini), the largest conformational differences, indicated by <i>arrows</i>, between the two catalytic domains, are the hairpin loop between strands <i>β</i>10 and <i>β</i>11 (containing motif VIII) and the lid for the entrance to the cofactor binding (containing motif X). Superposition of yeast Dot1p and human Dot1L (<i>bottom panel</i>), indicating a hinge movement between two domains, possibly caused by the binding of the Arg (see Fig. 4<i>C</i>). <i>F</i>, superimposition of the hairpin loop conformations in yeast Dot1p and human Dot1L (in <i>parentheses</i>).</div>
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|
||
Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Saccharomyces cerevisiae Proteins / chemistry*"
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Saccharomyces cerevisiae Proteins / chemistry*
|
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</button><div id="keyword-actions-mesh-terms-major-28"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Saccharomyces cerevisiae Proteins / chemistry*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Saccharomyces+cerevisiae+Proteins%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Saccharomyces+cerevisiae+Proteins%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc"
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Search in MeSH
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Sequence Homology, Amino Acid
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aria-label="Dropdown menu for keyword Sequence Homology, Amino Acid"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Dropdown menu for keyword Ultraviolet Rays"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li></ul>
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</div>
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|
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<div id="substances" class="substances keywords-section">
|
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<h2 class="title">
|
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Substances
|
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</h2>
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cross-Linking Reagents"
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tabindex="0"
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Cross-Linking Reagents
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</button><div id="keyword-actions-substances-0"
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hidden
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aria-label="Dropdown menu for keyword Cross-Linking Reagents"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cross-Linking+Reagents%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cross-Linking+Reagents%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Cross-Linking Reagents"[nm]"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cross-Linking Reagents"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Fungal Proteins"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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Fungal Proteins
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</button><div id="keyword-actions-substances-1"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
||
aria-label="Dropdown menu for keyword Fungal Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Fungal+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Fungal+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Fungal Proteins"[nm]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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data-search-term=""Fungal Proteins"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Fungal Proteins"[nm]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Histones"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-2"
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aria-expanded="false"
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data-pinger-ignore>
|
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Histones
|
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</button><div id="keyword-actions-substances-2"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Histones"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Histones%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Histones%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Histones"[nm]"
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Search in PubMed
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Search in MeSH
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data-search-term=""Histones"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Histones"[nm]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Nuclear Proteins"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-3"
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aria-expanded="false"
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data-pinger-ignore>
|
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Nuclear Proteins
|
||
</button><div id="keyword-actions-substances-3"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
||
aria-label="Dropdown menu for keyword Nuclear Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Nuclear+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Nuclear+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Nuclear Proteins"[nm]"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Nuclear Proteins"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Nuclear Proteins"[nm]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Nucleosomes"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-4"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Nucleosomes
|
||
</button><div id="keyword-actions-substances-4"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Nucleosomes"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Nucleosomes%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Nucleosomes%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Nucleosomes"[nm]"
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data-ga-label="Nucleosomes">
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Search in PubMed
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Nucleosomes%22"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
|
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data-search-term=""Nucleosomes"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Nucleosomes"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Recombinant Proteins"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-5"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Recombinant Proteins
|
||
</button><div id="keyword-actions-substances-5"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Recombinant Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Recombinant+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Recombinant+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Recombinant Proteins"[nm]"
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data-ga-label="Recombinant Proteins">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Recombinant Proteins"[nm]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Recombinant Proteins"[nm]"
|
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Saccharomyces cerevisiae Proteins"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-6"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Saccharomyces cerevisiae Proteins
|
||
</button><div id="keyword-actions-substances-6"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Saccharomyces cerevisiae Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Saccharomyces+cerevisiae+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Saccharomyces+cerevisiae+Proteins%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Saccharomyces cerevisiae Proteins"[nm]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Saccharomyces+cerevisiae+Proteins%22"
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Saccharomyces cerevisiae Proteins"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Saccharomyces cerevisiae Proteins"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Glutamine"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-7"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Glutamine
|
||
</button><div id="keyword-actions-substances-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Glutamine"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Glutamine%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Glutamine%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Glutamine"[nm]"
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||
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||
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||
|
||
|
||
|
||
<div id="supplemental-data" class="supplemental-data">
|
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<h2 class="title">
|
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Associated data
|
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</h2>
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<div id="related-links" class="related-links">
|
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<h2 class="title">
|
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Related information
|
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</h2>
|
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|
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<ul class="related-links-list"><li><a title="Link to related CDD entry" href="https://www.ncbi.nlm.nih.gov/cdd?linkname=pubmed_cdd&from_uid=15292170"
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Domains
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</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&from_uid=15292170"
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Gene
|
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</a></li><li><a title="Published protein sequences" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein&from_uid=15292170"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=15292170&ordinalpos=1&linkpos=3">
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Protein
|
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</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=15292170"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=15292170&ordinalpos=1&linkpos=4">
|
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Protein (RefSeq)
|
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</a></li><li><a title="Protein family models supported by a particular publication" href="https://www.ncbi.nlm.nih.gov/protfam?linkname=pubmed_protfam&from_uid=15292170"
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=15292170&ordinalpos=1&linkpos=5">
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Protein Family Models
|
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</a></li><li><a title="Related PubChem Compound" href="https://www.ncbi.nlm.nih.gov/pccompound?linkname=pubmed_pccompound&from_uid=15292170"
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PubChem Compound
|
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</a></li><li><a title="Related PubChem Compound via MeSH" href="https://www.ncbi.nlm.nih.gov/pccompound?linkname=pubmed_pccompound_mesh&from_uid=15292170"
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PubChem Compound (MeSH Keyword)
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|
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PubChem Substance
|
||
</a></li><li><a title="Published 3D structures" href="https://www.ncbi.nlm.nih.gov/structure?linkname=pubmed_structure&from_uid=15292170"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=15292170&ordinalpos=1&linkpos=9">
|
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Structure
|
||
</a></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="grants" class="grants">
|
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<h2 class="title">
|
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Grants and funding
|
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</h2>
|
||
<div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a
|
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title="All articles for grant GM61355/GM/NIGMS NIH HHS/United States"
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