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Hydrolase PDB-id
1qh5
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Description
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References
PROCHECK
Protein chains
260 a.a. *
Ligands
GTT
GBP
Metal ions
_ZN ×4
Waters ×357

* Residue conservation analysis
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PDB id: 1qh5
Name: Hydrolase
Title: Human glyoxalase ii with s-(n-hydroxy-n- bromophenylcarbamoyl)glutathione

Structure:
Protein (hydroxyacylglutathione hydrolase). Chain: a, b. Synonym: glyoxalase ii. Engineered: yes

Source:
Homo sapiens. Human. Organism_taxid: 9606. Tissue: liver. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: heterologously expressed

UniProt:
Chains A, B: Q16775 (GLO2_HUMAN)
Pfam   ArchSchema ?
Seq: 260 a.a.
Struc: 260 a.a.
Key:    PfamA domain
 Secondary structure  CATH domain

Enzyme class:
E.C.3.1.2.6   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:
S-(2-hydroxyacyl)glutathione + H2O = glutathione + a 2-hydroxy carboxylate (see diagram below)

Resolution:
1.45Å

R-factor:
0.204

R-free:
0.232

Authors:
A.D.Cameron,M.Ridderstrom,B.Olin,B.Mannervik

Key ref:
A.D.Cameron et al. (1999). Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue.. Structure, 7, 1067-1078. [PubMed id: 10508780] [DOI: 10.1016/S0969-2126(99)80174-9]

Date:
11-May-99

Release date:
24-Sep-99

Related entries:
1qh3
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Enzyme reaction for E.C.3.1.2.6


(S)-(2-hydroxyacyl)glutathione
Bound ligand (Het Group name = GBP)
matches with 64.00% similarity
+ H(2)O
=

glutathione
Bound ligand (Het Group name = GTT)
corresponds exactly
+ a 2-hydroxy acid anion
Molecule diagrams generated from .mol files obtained from the KEGG ftp site.

 
    Key reference    
 
 
DOI no: 10.1016/S0969-2126(99)80174-9 Structure 7:1067-1078 (1999)
PubMed id: 10508780  
 
 
Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue.
A.D.Cameron, M.Ridderström, B.Olin, B.Mannervik.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19535341 V.Sauvé, P.Roversi, K.J.Leath, E.F.Garman, R.Antrobus, S.M.Lea, and B.C.Berks (2009).
Mechanism for the Hydrolysis of a Sulfur-Sulfur Bond Based on the Crystal Structure of the Thiosulfohydrolase SoxB.
  J Biol Chem, 284, 21707-21718.
PDB codes: 2wdc 2wdd 2wde 2wdf
18625687 A.Y.Peleg, H.Seifert, and D.L.Paterson (2008).
Acinetobacter baumannii: emergence of a successful pathogen.
  Clin Microbiol Rev, 21, 538-582.  
17360274 Y.H.Dong, L.Y.Wang, and L.H.Zhang (2007).
Quorum-quenching microbial infections: mechanisms and implications.
  Philos Trans R Soc Lond B Biol Sci, 362, 1201-1211.  
17363966 Y.Redko, I.Li de Lasierra-Gallay, and C.Condon (2007).
When all's zed and done: the structure and function of RNase Z in prokaryotes.
  Nat Rev Microbiol, 5, 278-286.  
16439663 H.S.Park, S.H.Nam, J.K.Lee, C.N.Yoon, B.Mannervik, S.J.Benkovic, and H.S.Kim (2006).
Design and evolution of new catalytic activity with an existing protein scaffold.
  Science, 311, 535-538.
PDB code: 2f50
16929096 J.G.McCoy, C.A.Bingman, E.Bitto, M.M.Holdorf, C.A.Makaroff, and G.N.Phillips (2006).
Structure of an ETHE1-like protein from Arabidopsis thaliana.
  Acta Crystallogr D Biol Crystallogr, 62, 964-970.
PDB code: 2gcu
  16880563 J.Trincão, M.Sousa Silva, L.Barata, C.Bonifácio, S.Carvalho, A.M.Tomás, A.E.Ferreira, C.Cordeiro, A.Ponces Freire, and M.J.Romão (2006).
Purification, crystallization and preliminary X-ray diffraction analysis of the glyoxalase II from Leishmania infantum.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 805-807.  
16527816 J.Wang, Y.Okamoto, J.Morishita, K.Tsuboi, A.Miyatake, and N.Ueda (2006).
Functional analysis of the purified anandamide-generating phospholipase D as a member of the metallo-beta-lactamase family.
  J Biol Chem, 281, 12325-12335.  
16357976 L.M.Berreau, A.Saha, and A.M.Arif (2006).
Thioester hydrolysis reactivity of zinc hydroxide complexes: investigating reactivity relevant to glyoxalase II enzymes.
  Dalton Trans, 0, 183-192.  
16183799 V.Tiranti, E.Briem, E.Lamantea, R.Mineri, E.Papaleo, L.De Gioia, F.Forlani, P.Rinaldo, P.Dickson, B.Abu-Libdeh, L.Cindro-Heberle, M.Owaidha, R.M.Jack, E.Christensen, A.Burlina, and M.Zeviani (2006).
ETHE1 mutations are specific to ethylmalonic encephalopathy.
  J Med Genet, 43, 340-346.  
16336119 A.Vogel, O.Schilling, B.Späth, and A.Marchfelder (2005).
The tRNase Z family of proteins: physiological functions, substrate specificity and structural properties.
  Biol Chem, 386, 1253-1264.  
16087890 D.Liu, B.W.Lepore, G.A.Petsko, P.W.Thomas, E.M.Stone, W.Fast, and D.Ringe (2005).
Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis.
  Proc Natl Acad Sci U S A, 102, 11882-11887.
PDB code: 2a7m
15980349 G.Garau, A.M.Di Guilmi, and B.G.Hall (2005).
Structure-based phylogeny of the metallo-beta-lactamases.
  Antimicrob Agents Chemother, 49, 2778-2784.  
15908436 G.Garau, D.Lemaire, T.Vernet, O.Dideberg, and A.M.Di Guilmi (2005).
Crystal structure of phosphorylcholine esterase domain of the virulence factor choline-binding protein e from streptococcus pneumoniae: new structural features among the metallo-beta-lactamase superfamily.
  J Biol Chem, 280, 28591-28600.
PDB codes: 1wra 2v05
16227621 G.P.Marasinghe, I.M.Sander, B.Bennett, G.Periyannan, K.W.Yang, C.A.Makaroff, and M.W.Crowder (2005).
Structural studies on a mitochondrial glyoxalase II.
  J Biol Chem, 280, 40668-40675.
PDB code: 1xm8
15654328 I.L.de la Sierra-Gallay, O.Pellegrini, and C.Condon (2005).
Structural basis for substrate binding, cleavage and allostery in the tRNA maturase RNase Z.
  Nature, 433, 657-661.
PDB code: 1y44
15895092 J.A.Hermoso, L.Lagartera, A.González, M.Stelter, P.García, M.Martínez-Ripoll, J.L.García, and M.Menéndez (2005).
Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce.
  Nat Struct Mol Biol, 12, 533-538.
PDB code: 2bib
16260756 L.Lagartera, A.González, J.A.Hermoso, J.L.Saíz, P.García, J.L.García, and M.Menéndez (2005).
Pneumococcal phosphorylcholine esterase, Pce, contains a metal binuclear center that is essential for substrate binding and catalysis.
  Protein Sci, 14, 3013-3024.  
15843146 M.Akoachere, R.Iozef, S.Rahlfs, M.Deponte, B.Mannervik, D.J.Creighton, H.Schirmer, and K.Becker (2005).
Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts.
  Biol Chem, 386, 41-52.  
15699034 O.Schilling, B.Späth, B.Kostelecky, A.Marchfelder, W.Meyer-Klaucke, and A.Vogel (2005).
Exosite modules guide substrate recognition in the ZiPD/ElaC protein family.
  J Biol Chem, 280, 17857-17862.  
15296518 R.I.Sadreyev, and N.V.Grishin (2004).
Estimates of statistical significance for comparison of individual positions in multiple sequence alignments.
  BMC Bioinformatics, 5, 106.  
14976196 T.Irsch, and R.L.Krauth-Siegel (2004).
Glyoxalase II of African trypanosomes is trypanothione-dependent.
  J Biol Chem, 279, 22209-22217.  
14634025 Y.Okamoto, J.Morishita, K.Tsuboi, T.Tonai, and N.Ueda (2004).
Molecular characterization of a phospholipase D generating anandamide and its congeners.
  J Biol Chem, 279, 5298-5305.  
12574165 M.E.Meima, K.E.Weening, and P.Schaap (2003).
Characterization of a cAMP-stimulated cAMP phosphodiesterase in Dictyostelium discoideum.
  J Biol Chem, 278, 14356-14362.  
12824499 R.M.Rasia, M.Ceolín, and A.J.Vila (2003).
Grafting a new metal ligand in the cocatalytic site of B. cereus metallo-beta-lactamase: structural flexibility without loss of activity.
  Protein Sci, 12, 1538-1546.  
12029081 A.Vogel, O.Schilling, M.Niecke, J.Bettmer, and W.Meyer-Klaucke (2002).
ElaC encodes a novel binuclear zinc phosphodiesterase.
  J Biol Chem, 277, 29078-29085.  
11847294 C.M.Gomes, C.Frazão, A.V.Xavier, J.Legall, and M.Teixeira (2002).
Functional control of the binuclear metal site in the metallo-beta-lactamase-like fold by subtle amino acid replacements.
  Protein Sci, 11, 707-712.  
12429831 M.E.Meima, R.M.Biondi, and P.Schaap (2002).
Identification of a novel type of cGMP phosphodiesterase that is defective in the chemotactic stmF mutants.
  Mol Biol Cell, 13, 3870-3877.  
  10933508 L.Chantalat, E.Duée, M.Galleni, J.M.Frère, and O.Dideberg (2000).
Structural effects of the active site mutation cysteine to serine in Bacillus cereus zinc-beta-lactamase.
  Protein Sci, 9, 1402-1406.
PDB code: 1dxk
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.