1qh3
From Proteopedia
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==Overview== | ==Overview== | ||
| - | BACKGROUND: Glyoxalase II, the second of two enzymes in the glyoxalase | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Hydroxyacylglutathione hydrolase]] | [[Category: Hydroxyacylglutathione hydrolase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cameron, A | + | [[Category: Cameron, A D.]] |
[[Category: Mannervik, B.]] | [[Category: Mannervik, B.]] | ||
[[Category: Olin, B.]] | [[Category: Olin, B.]] | ||
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[[Category: metallo-hydrolase]] | [[Category: metallo-hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:39:29 2008'' |
Revision as of 12:39, 21 February 2008
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HUMAN GLYOXALASE II WITH CACODYLATE AND ACETATE IONS PRESENT IN THE ACTIVE SITE
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Glyoxalase II deficiency OMIM:[138760]
About this Structure
1QH3 is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Hydroxyacylglutathione hydrolase, with EC number 3.1.2.6 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 14:39:29 2008
Categories: Homo sapiens | Hydroxyacylglutathione hydrolase | Single protein | Cameron, A D. | Mannervik, B. | Olin, B. | Ridderstrom, M. | ACT | CAC | CL | MN | ZN | Metallo-hydrolase
