Structural basis for detoxification and oxidative stress protection in membranes
- PMID: 16806268
- DOI: 10.1016/j.jmb.2006.05.056
Structural basis for detoxification and oxidative stress protection in membranes
Abstract
Synthesis of mediators of fever, pain and inflammation as well as protection against reactive molecules and oxidative stress is a hallmark of the MAPEG superfamily (membrane associated proteins in eicosanoid and glutathione metabolism). The structure of a MAPEG member, rat microsomal glutathione transferase 1, at 3.2 A resolution, solved here in complex with glutathione by electron crystallography, defines the active site location and a cytosolic domain involved in enzyme activation. The glutathione binding site is found to be different from that of the canonical soluble glutathione transferases. The architecture of the homotrimer supports a catalytic mechanism involving subunit interactions and reveals both cytosolic and membraneous substrate entry sites, providing a rationale for the membrane location of the enzyme.
Similar articles
-
The structure of membrane associated proteins in eicosanoid and glutathione metabolism as determined by electron crystallography.Curr Opin Struct Biol. 2007 Aug;17(4):396-404. doi: 10.1016/j.sbi.2007.07.008. Epub 2007 Sep 17. Curr Opin Struct Biol. 2007. PMID: 17870465 Review.
-
Parallel evolutionary pathways for glutathione transferases: structure and mechanism of the mitochondrial class kappa enzyme rGSTK1-1.Biochemistry. 2004 Jan 20;43(2):352-61. doi: 10.1021/bi035832z. Biochemistry. 2004. PMID: 14717589
-
Crystallographic and functional characterization of the fluorodifen-inducible glutathione transferase from Glycine max reveals an active site topography suited for diphenylether herbicides and a novel L-site.J Mol Biol. 2009 Jan 23;385(3):984-1002. doi: 10.1016/j.jmb.2008.10.084. Epub 2008 Nov 6. J Mol Biol. 2009. PMID: 19014949
-
Three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate: catalytic roles of Cys10 and His106.J Mol Biol. 1998 Aug 7;281(1):135-47. doi: 10.1006/jmbi.1998.1927. J Mol Biol. 1998. PMID: 9680481
-
Microsomal glutathione transferase 1: mechanism and functional roles.Drug Metab Rev. 2011 May;43(2):300-6. doi: 10.3109/03602532.2011.558511. Drug Metab Rev. 2011. PMID: 21495795 Review.
Cited by
-
Glutathione S-Transferase (GST) Gene Diversity in the Crustacean Calanus finmarchicus--Contributors to Cellular Detoxification.PLoS One. 2015 May 6;10(5):e0123322. doi: 10.1371/journal.pone.0123322. eCollection 2015. PLoS One. 2015. PMID: 25945801 Free PMC article.
-
Understanding microscopic binding of human microsomal prostaglandin E synthase-1 (mPGES-1) trimer with substrate PGH2 and cofactor GSH: insights from computational alanine scanning and site-directed mutagenesis.J Phys Chem B. 2010 Apr 29;114(16):5605-16. doi: 10.1021/jp100668y. J Phys Chem B. 2010. PMID: 20369883 Free PMC article.
-
EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites.PLoS Biol. 2019 Sep 30;17(9):e3000473. doi: 10.1371/journal.pbio.3000473. eCollection 2019 Sep. PLoS Biol. 2019. PMID: 31568532 Free PMC article.
-
A helical processing pipeline for EM structure determination of membrane proteins.Methods. 2011 Dec;55(4):350-62. doi: 10.1016/j.ymeth.2011.09.013. Epub 2011 Sep 20. Methods. 2011. PMID: 21964395 Free PMC article. Review.
-
Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation.Sci Rep. 2017 Aug 11;7(1):7897. doi: 10.1038/s41598-017-07912-3. Sci Rep. 2017. PMID: 28801553 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
