1qh5
HUMAN GLYOXALASE II WITH S-(N-HYDROXY-N-BROMOPHENYLCARBAMOYL)GLUTATHIONE
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OverviewOverview
BACKGROUND: Glyoxalase II, the second of two enzymes in the glyoxalase, system, is a thiolesterase that catalyses the hydrolysis of, S-D-lactoylglutathione to form glutathione and D-lactic acid. RESULTS: The, structure of human glyoxalase II was solved initially by single, isomorphous replacement with anomalous scattering and refined at a, resolution of 1.9 A. The enzyme consists of two domains. The first domain, folds into a four-layered beta sandwich, similar to that seen in the, metallo-beta-lactamases. The second domain is predominantly alpha-helical., The active site contains a binuclear zinc-binding site and a, substrate-binding site extending over the domain interface. The model, contains acetate and cacodylate in the active site. A second complex was, derived from crystals soaked in a solution containing the slow substrate, S-(N-hydroxy-N-bromophenylcarbamoyl)glutathione. This complex was refined, at a resolution of 1.45 A. It contains the added ligand in one molecule of, the asymmetric unit and glutathione in the other. CONCLUSIONS: The, arrangement of ligands around the zinc ions includes a water molecule, presumably in the form of a hydroxide ion, coordinated to both metal ions., This hydroxide ion is situated 2.9 A from the carbonyl carbon of the, substrate in such a position that it could act as the nucleophile during, catalysis. The reaction mechanism may also have implications for the, action of metallo-beta-lactamases.
DiseaseDisease
Known diseases associated with this structure: Glyoxalase II deficiency OMIM:[138760]
About this StructureAbout this Structure
1QH5 is a Single protein structure of sequence from Homo sapiens with ZN, GTT and GBP as ligands. Active as Hydroxyacylglutathione hydrolase, with EC number 3.1.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue., Cameron AD, Ridderstrom M, Olin B, Mannervik B, Structure. 1999 Sep 15;7(9):1067-78. PMID:10508780
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