2qmc
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(New page: 200px<br /><applet load="2qmc" size="350" color="white" frame="true" align="right" spinBox="true" caption="2qmc, resolution 1.550Å" /> '''Crystal Structure o...)
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Revision as of 06:21, 13 February 2008
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Crystal Structure of Helicobacter Pylori Gamma-Glutamyltranspeptidase T380A Mutant
Overview
Helicobacter pylori gamma-glutamyltranspeptidase (HpGT) is a member of the, N-terminal nucleophile hydrolase superfamily. It is translated as an, inactive 60 kDa polypeptide precursor that undergoes intramolecular, autocatalytic cleavage to generate a fully active heterodimer composed of, a 40 kDa and a 20 kDa subunit. The resultant N-terminus, Thr 380, has been, shown to be the catalytic nucleophile in both autoprocessing and enzymatic, reactions. Once processed, HpGT catalyzes the hydrolysis of the, gamma-glutamyl bond in glutathione and its conjugates. To facilitate the, determination of physiologically relevant substrates for the enzyme, crystal structures of HpGT in complex with glutamate (1.6 A, Rfactor =, 16.7%, Rfree = 19.0%) and an inactive HpGT mutant, T380A, in complex with, S-(nitrobenzyl)glutathione (1.55 A, Rfactor = 18.7%, Rfree = 21.8%) have, been determined. Residues that comprise the gamma-glutamyl binding site, are primarily located in the 20 kDa subunit and make numerous hydrogen, bonds with the alpha-amino and alpha-carboxylate groups of the substrate., In contrast, a single hydrogen bond occurs between the T380A mutant and, the remainder of the ligand. Lack of specific coordination beyond the, gamma-glutamyl moiety may account for the substrate binding permissiveness, of the enzyme. Structural analysis was combined with site-directed, mutagenesis of residues involved in maintaining the conformation of a loop, region that covers the gamma-glutamyl binding site. Results provide, evidence that access to this buried site may occur through conformational, changes in the Tyr 433-containing loop, as disruption of the intricate, hydrogen-bond network responsible for optimal placement of Tyr 433, significantly diminishes catalytic activity.
About this Structure
2QMC is a Protein complex structure of sequences from Helicobacter pylori with as ligand. Active as Gamma-glutamyltransferase, with EC number 2.3.2.2 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Characterization of Helicobacter pylori gamma-glutamyltranspeptidase reveals the molecular basis for substrate specificity and a critical role for the tyrosine 433-containing loop in catalysis., Morrow AL, Williams K, Sand A, Boanca G, Barycki JJ, Biochemistry. 2007 Nov 20;46(46):13407-14. Epub 2007 Oct 26. PMID:17960917
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