PMID- 10508780
OWN - NLM
STAT- MEDLINE
DCOM- 19991215
LR  - 20131121
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 7
IP  - 9
DP  - 1999 Sep 15
TI  - Crystal structure of human glyoxalase II and its complex with a glutathione
      thiolester substrate analogue.
PG  - 1067-78
AB  - 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.
FAU - Cameron, A D
AU  - Cameron AD
AD  - Department of Molecular Biology Uppsala University Biomedical Center Box 590,
      S-751 24, Uppsala, Sweden Structural Biology Laboratory Department of Chemistry
      University of York Heslington, York, UK YO10 5DD,. cameron@yorvic.york.ac.uk.
FAU - Ridderstrom, M
AU  - Ridderstrom M
FAU - Olin, B
AU  - Olin B
FAU - Mannervik, B
AU  - Mannervik B
LA  - eng
SI  - PDB/1QH3
SI  - PDB/1QH5
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (Acetates)
RN  - 0 (Metals)
RN  - 0 (S-(N-hydroxy-N-bromophenylcarbamoyl)glutathione)
RN  - AJ2HL7EU8K (Cacodylic Acid)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.6 (hydroxyacylglutathione hydrolase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Acetates/chemistry/metabolism
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Cacodylic Acid/chemistry
MH  - Conserved Sequence
MH  - Crystallography, X-Ray
MH  - Glutathione/*analogs & derivatives/chemistry/metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Metals/metabolism
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - Substrate Specificity
MH  - Thiolester Hydrolases/*chemistry/*metabolism
EDAT- 1999/10/06 00:00
MHDA- 1999/10/06 00:01
CRDT- 1999/10/06 00:00
PHST- 1999/10/06 00:00 [pubmed]
PHST- 1999/10/06 00:01 [medline]
PHST- 1999/10/06 00:00 [entrez]
AID - S0969-2126(99)80174-9 [pii]
PST - ppublish
SO  - Structure. 1999 Sep 15;7(9):1067-78.