Unique regulation of the active site of the serine esterase S-formylglutathione hydrolase.

Journal of Molecular Biology
Ian CumminsRobert Edwards

Abstract

S-Formylglutathione hydrolases (SFGHs) are highly conserved thioesterases present in prokaryotes and eukaryotes, and form part of the formaldehyde detoxification pathway, as well as functioning as xenobiotic-hydrolysing carboxyesterases. As defined by their sensitivity to covalent modification, SFGHs behave as cysteine hydrolases, being inactivated by thiol alkylating agents, while being insensitive to inhibition by organophosphates such as paraoxon. As such, the enzyme has been classified as an esterase D in animals, plants and microbes. While SFGHs do contain a conserved cysteine residue that has been implicated in catalysis, sequence analysis also reveals the classic catalytic triad of a serine hydrolase. Using a combination of selective protein modification and X-ray crystallography, AtSFGH from Arabidopsis thaliana has been shown to be a serine hydrolase rather than a cysteine hydrolase. Uniquely, the conserved reactive cysteine (Cys59) previously implicated in catalysis lies in close proximity to the serine hydrolase triad, serving a gate-keeping function in comprehensively regulating access to the active site. Thus, any covalent modification of Cys59 inhibited all hydrolase activities of the enzyme. When isolated from Es...Continue Reading

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Citations

Jul 23, 2011·The Journal of Biological Chemistry·Mark SkipseyRobert Edwards
Jan 26, 2013·PloS One·Rohan Bythell-DouglasCharles S Bond
Mar 15, 2016·Frontiers in Microbiology·Nathan H ChenAlastair G McEwan
Aug 5, 2009·Protein Science : a Publication of the Protein Society·Karin E van StraatenDavid A R Sanders
Apr 3, 2008·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Dirk Hertel, Heinz Bässler
Apr 21, 2010·Proteomics·Christophe H MarchandPaulette Decottignies
May 14, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Angelika BondzioRalf Einspanier
Nov 29, 2017·Oncotarget·Yuechi Xu, Zhongjie Sun
Sep 18, 2020·Scientific Reports·Achintya Kumar DoluiPanneerselvam Vijayaraj
Feb 23, 2021·Journal of Cellular Physiology·Xinpeng ChenJunying Miao
May 18, 2020·Progress in Lipid Research·Crystall M D SwarbrickJade K Forwood
Mar 16, 2021·Frontiers in Immunology·Kangli LiHaixue Zheng
Feb 20, 2009·Chemical Research in Toxicology·Adriaan W TuinDaan Noort
Aug 22, 2012·Archives of Biochemistry and Biophysics·Patricia M LeglerCharles B Millard

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