The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450 functional hybrid
- PMID: 8747463
- DOI: 10.1016/s0969-2126(01)00274-x
The crystal structure of chloroperoxidase: a heme peroxidase--cytochrome P450 functional hybrid
Abstract
Background: Chloroperoxidase (CPO) is a versatile heme-containing enzyme that exhibits peroxidase, catalase and cytochrome P450-like activities in addition to catalyzing halogenation reactions. The structure determination of CPO was undertaken to help elucidate those structural features that enable the enzyme to exhibit these multiple activities.
Results: Despite functional similarities with other heme enzymes, CPO folds into a novel tertiary structure dominated by eight helical segments. The catalytic base, required to cleave the peroxide O-O bond, is glutamic acid rather than histidine as in other peroxidases. CPO contains a hydrophobic patch above the heme that could be the binding site for substrates that undergo P450-like reactions. The crystal structure also shows extensive glycosylation with both N- and O-linked glycosyl chains.
Conclusions: The proximal side of the heme in CPO resembles cytochrome P450 because a cysteine residue serves as an axial heme ligand, whereas the distal side of the heme is 'peroxidase-like' in that polar residues form the peroxide-binding site. Access to the heme pocket is restricted to the distal face such that small organic substrates can interact with the iron-linked oxygen atom which accounts for the P450-like reactions catalyzed by chloroperoxidase.
Similar articles
-
Stereochemistry of the chloroperoxidase active site: crystallographic and molecular-modeling studies.Chem Biol. 1998 Sep;5(9):461-73. doi: 10.1016/s1074-5521(98)90003-5. Chem Biol. 1998. PMID: 9751642
-
Modification of the heme active site to increase the peroxidase activity of thermophilic cytochrome P450: a rational approach.J Inorg Biochem. 2010 Nov;104(11):1185-94. doi: 10.1016/j.jinorgbio.2010.07.008. Epub 2010 Jul 23. J Inorg Biochem. 2010. PMID: 20709408
-
Replacement of the proximal heme thiolate ligand in chloroperoxidase with a histidine residue.Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12412-7. doi: 10.1073/pnas.96.22.12412. Proc Natl Acad Sci U S A. 1999. PMID: 10535936 Free PMC article.
-
Heme-thiolate haloperoxidases: versatile biocatalysts with biotechnological and environmental significance.Appl Microbiol Biotechnol. 2006 Jul;71(3):276-88. doi: 10.1007/s00253-006-0417-3. Appl Microbiol Biotechnol. 2006. PMID: 16628447 Review.
-
Fungal unspecific peroxygenases: heme-thiolate proteins that combine peroxidase and cytochrome p450 properties.Adv Exp Med Biol. 2015;851:341-68. doi: 10.1007/978-3-319-16009-2_13. Adv Exp Med Biol. 2015. PMID: 26002742 Review.
Cited by
-
The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies.Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3569-74. doi: 10.1073/pnas.0830019100. Epub 2003 Mar 24. Proc Natl Acad Sci U S A. 2003. PMID: 12655056 Free PMC article. Review.
-
Structural perspective on enzymatic halogenation.Acc Chem Res. 2009 Jan 20;42(1):147-55. doi: 10.1021/ar800088r. Acc Chem Res. 2009. PMID: 18774824 Free PMC article. Review.
-
Processing of predicted substrates of fungal Kex2 proteinases from Candida albicans, C. glabrata, Saccharomyces cerevisiae and Pichia pastoris.BMC Microbiol. 2008 Jul 14;8:116. doi: 10.1186/1471-2180-8-116. BMC Microbiol. 2008. PMID: 18625069 Free PMC article.
-
Two New Unspecific Peroxygenases from Heterologous Expression of Fungal Genes in Escherichia coli.Appl Environ Microbiol. 2020 Mar 18;86(7):e02899-19. doi: 10.1128/AEM.02899-19. Print 2020 Mar 18. Appl Environ Microbiol. 2020. PMID: 31980430 Free PMC article.
-
Mössbauer and electron paramagnetic resonance studies of chloroperoxidase following mechanism-based inactivation with allylbenzene.Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12791-8. doi: 10.1073/pnas.93.23.12791. Proc Natl Acad Sci U S A. 1996. PMID: 8917498 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources