5b5t
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Escherichia coli Gamma-Glutamyltranspeptidase in Complex with peptidyl phosphonate inhibitor 1b== | |
| + | <StructureSection load='5b5t' size='340' side='right' caption='[[5b5t]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5b5t]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B5T FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6FY:(2~{S})-2-AZANYL-4-[(2~{R})-1-(2-HYDROXY-2-OXOETHYLAMINO)-1-OXIDANYLIDENE-BUTAN-2-YL]OXYPHOSPHONOYL-BUTANOIC+ACID'>6FY</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5b5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b5t OCA], [http://pdbe.org/5b5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b5t RCSB], [http://www.ebi.ac.uk/pdbsum/5b5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b5t ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | gamma-Glutamyl transpeptidase (GGT, EC 2.3.2.2) that catalyzes the hydrolysis and transpeptidation of glutathione and its S-conjugates is involved in a number of physiological and pathological processes through glutathione metabolism and is an attractive pharmaceutical target. We report here the evaluation of a phosphonate-based irreversible inhibitor, 2-amino-4-{[3-(carboxymethyl)phenoxy](methoyl)phosphoryl}butanoic acid (GGsTop) and its analogues as a mechanism-based inhibitor of human GGT. GGsTop is a stable compound, but inactivated the human enzyme significantly faster than the other phosphonates, and importantly did not inhibit a glutamine amidotransferase. The structure-activity relationships, X-ray crystallography with Escherichia coli GGT, sequence alignment and site-directed mutagenesis of human GGT revealed a critical electrostatic interaction between the terminal carboxylate of GGsTop and the active-site residue Lys562 of human GGT for potent inhibition. GGsTop showed no cytotoxicity toward human fibroblasts and hepatic stellate cells up to 1mM. GGsTop serves as a non-toxic, selective and highly potent irreversible GGT inhibitor that could be used for various in vivo as well as in vitro biochemical studies. | ||
| - | + | Phosphonate-based irreversible inhibitors of human gamma-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity.,Kamiyama A, Nakajima M, Han L, Wada K, Mizutani M, Tabuchi Y, Kojima-Yuasa A, Matsui-Yuasa I, Suzuki H, Fukuyama K, Watanabe B, Hiratake J Bioorg Med Chem. 2016 Aug 31. pii: S0968-0896(16)30667-8. doi:, 10.1016/j.bmc.2016.08.050. PMID:27622749<ref>PMID:27622749</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5b5t" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Fukuyama, K]] | [[Category: Fukuyama, K]] | ||
| + | [[Category: Wada, K]] | ||
| + | [[Category: Glutathione]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 16:49, 3 October 2016
Crystal Structure of Escherichia coli Gamma-Glutamyltranspeptidase in Complex with peptidyl phosphonate inhibitor 1b
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