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Hydrolase PDB id
1qh5
Jmol
Contents
Protein chains
260 a.a. *
Ligands
GSH
GBP
Metals
_ZN ×4
Waters ×357
* Residue conservation analysis
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
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q16775  (GLO2_HUMAN) -  Hydroxyacylglutathione hydrolase, mitochondrial
Seq:
Struc: 		308 a.a.
260 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.2.6  - Hydroxyacylglutathione hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-(2-hydroxyacyl)glutathione + H2O = glutathione + a 2-hydroxy carboxylate
S-(2-hydroxyacyl)glutathione
Bound ligand (Het Group name = GBP)
matches with 64.71% similarity 		+ H(2)O
 =
glutathione
Bound ligand (Het Group name = GSH)
corresponds exactly 		+ 2-hydroxy carboxylate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     hydrolase activity     3 terms  

 

 
    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
21310259 M.Urscher, R.Alisch, and M.Deponte (2011).
The glyoxalase system of malaria parasites-Implications for cell biology and general glyoxalase research.
  Semin Cell Dev Biol, 22, 262-270.  
21320620 M.Xue, N.Rabbani, and P.J.Thornalley (2011).
Glyoxalase in ageing.
  Semin Cell Dev Biol, 22, 293-301.  
21310261 S.Wyllie, and A.H.Fairlamb (2011).
Methylglyoxal metabolism in trypanosomes and leishmania.
  Semin Cell Dev Biol, 22, 271-277.  
21310258 U.Suttisansanee, and J.F.Honek (2011).
Bacterial glyoxalase enzymes.
  Semin Cell Dev Biol, 22, 285-292.  
20669241 A.L.Stamp, P.Owen, K.E.Omari, C.E.Nichols, M.Lockyer, H.K.Lamb, I.G.Charles, A.R.Hawkins, and D.K.Stammers (2010).
Structural and functional characterization of Salmonella enterica serovar Typhimurium YcbL: an unusual Type II glyoxalase.
  Protein Sci, 19, 1897-1905.
PDB code: 2xf4
20506386 D.C.Cantu, Y.Chen, and P.J.Reilly (2010).
Thioesterases: a new perspective based on their primary and tertiary structures.
  Protein Sci, 19, 1281-1295.  
20535505 V.A.Campos-Bermudez, J.M.González, D.L.Tierney, and A.J.Vila (2010).
Spectroscopic signature of a ubiquitous metal binding site in the metallo-β-lactamase superfamily.
  J Biol Inorg Chem, 15, 1209-1218.  
20385411 V.A.Campos-Bermudez, J.Morán-Barrio, A.J.Costa-Filho, and A.J.Vila (2010).
Metal-dependent inhibition of glyoxalase II: a possible mechanism to regulate the enzyme activity.
  J Inorg Biochem, 104, 726-731.  
19663684 M.Urscher, and M.Deponte (2009).
Plasmodium falciparum glyoxalase II: Theorell-Chance product inhibition patterns, rate-limiting substrate binding via Arg(257)/Lys(260), and unmasking of acid-base catalysis.
  Biol Chem, 390, 1171-1183.  
19735113 P.Limphong, G.Nimako, P.W.Thomas, W.Fast, C.A.Makaroff, and M.W.Crowder (2009).
Arabidopsis thaliana mitochondrial glyoxalase 2-1 exhibits beta-lactamase activity.
  Biochemistry, 48, 8491-8493.  
18782082 P.Limphong, M.W.Crowder, B.Bennett, and C.A.Makaroff (2009).
Arabidopsis thaliana GLX2-1 contains a dinuclear metal binding site, but is not a glyoxalase 2.
  Biochem J, 417, 323-330.  
19549600 T.Awakawa, K.Yokota, N.Funa, F.Doi, N.Mori, H.Watanabe, and S.Horinouchi (2009).
Physically discrete beta-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase.
  Chem Biol, 16, 613-623.  
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.  
18656261 M.M.Holdorf, B.Bennett, M.W.Crowder, and C.A.Makaroff (2008).
Spectroscopic studies on Arabidopsis ETHE1, a glyoxalase II-like protein.
  J Inorg Biochem, 102, 1825-1830.  
18528987 N.Sharma, Z.Hu, M.W.Crowder, and B.Bennett (2008).
Conformational changes in the metallo-beta-lactamase ImiS during the catalytic reaction: an EPR spectrokinetic study of Co(II)-spin label interactions.
  J Am Chem Soc, 130, 8215-8222.  
17305336 M.Dal Peraro, A.J.Vila, P.Carloni, and M.L.Klein (2007).
Role of zinc content on the catalytic efficiency of B1 metallo beta-lactamases.
  J Am Chem Soc, 129, 2808-2816.  
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.  
11336668 D.Moshous, I.Callebaut, R.de Chasseval, B.Corneo, M.Cavazzana-Calvo, F.Le Deist, I.Tezcan, O.Sanal, Y.Bertrand, N.Philippe, A.Fischer, and J.P.de Villartay (2001).
Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency.
  Cell, 105, 177-186.  
  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 code is shown on the right.