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PDBsum entry 1qip

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
1qip
Jmol
Contents
Protein chain
176 a.a. *
Ligands
GNB ×4
BME ×4
Metals
_ZN ×4
Waters ×905
* Residue conservation analysis
PDB id:
1qip
Name: Lyase
Title: Human glyoxalase i complexed with s-p- nitrobenzyloxycarbonylglutathione
Structure: Protein (lactoylglutathione lyase). Chain: a, b, c, d. Synonym: glyoxalase i. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: heterologously expressed
Biol. unit: Dimer (from PQS)
Resolution:
1.72Å     R-factor:   0.170     R-free:   0.210
Authors: A.D.Cameron,M.Ridderstrom,B.Olin,B.Mannervik
Key ref:
A.D.Cameron et al. (1999). Reaction mechanism of glyoxalase I explored by an X-ray crystallographic analysis of the human enzyme in complex with a transition state analogue. Biochemistry, 38, 13480-13490. PubMed id: 10521255 DOI: 10.1021/bi990696c
Date:
14-Jun-99     Release date:   24-Nov-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q04760  (LGUL_HUMAN) -  Lactoylglutathione lyase
Seq:
Struc:
184 a.a.
176 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.4.1.5  - Lactoylglutathione lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (R)-S-lactoylglutathione = glutathione + methylglyoxal
(R)-S-lactoylglutathione
Bound ligand (Het Group name = GNB)
matches with 61.11% similarity
= glutathione
+
methylglyoxal
Bound ligand (Het Group name = BME)
matches with 50.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     carbohydrate metabolic process   6 terms 
  Biochemical function     lyase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi990696c Biochemistry 38:13480-13490 (1999)
PubMed id: 10521255  
 
 
Reaction mechanism of glyoxalase I explored by an X-ray crystallographic analysis of the human enzyme in complex with a transition state analogue.
A.D.Cameron, M.Ridderström, B.Olin, M.J.Kavarana, D.J.Creighton, B.Mannervik.
 
  ABSTRACT  
 
The structures of human glyoxalase I in complexes with S-(N-hydroxy-N-p-iodophenylcarbamoyl)glutathione (HIPC-GSH) and S-p-nitrobenzyloxycarbonylglutathione (NBC-GSH) have been determined at 2.0 and 1.72 A resolution, respectively. HIPC-GSH is a transition state analogue mimicking the enediolate intermediate that forms along the reaction pathway of glyoxalase I. In the structure, the hydroxycarbamoyl function is directly coordinated to the active site zinc ion. In contrast, the equivalent group in the NBC-GSH complex is approximately 6 A from the metal in a conformation that may resemble the product complex with S-D-lactoylglutathione. In this complex, two water molecules occupy the liganding positions at the zinc ion occupied by the hydroxycarbamoyl function in the enediolate analogue complex. Coordination of the transition state analogue to the metal enables a loop to close down over the active site, relative to its position in the product-like structure, allowing the glycine residue of the glutathione moiety to hydrogen bond with the protein. The structure of the complex with the enediolate analogue supports an "inner sphere mechanism" in which the GSH-methylglyoxal thiohemiacetal substrate is converted to product via a cis-enediolate intermediate. The zinc ion is envisioned to play an electrophilic role in catalysis by directly coordinating this intermediate. In addition, the carboxyl of Glu 172 is proposed to be displaced from the inner coordination sphere of the metal ion during substrate binding, thus allowing this group to facilitate proton transfer between the adjacent carbon atoms of the substrate. This proposal is supported by the observation that in the complex with the enediolate analogue the carboxyl group of Glu 172 is 3.3 A from the metal and is in an ideal position for reprotonation of the transition state intermediate. In contrast, Glu 172 is directly coordinated to the zinc ion in the complexes with S-benzylglutathione and with NBC-GSH.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20454679 G.Birkenmeier, C.Stegemann, R.Hoffmann, R.Günther, K.Huse, and C.Birkemeyer (2010).
Posttranslational modification of human glyoxalase 1 indicates redox-dependent regulation.
  PLoS One, 5, e10399.  
19710909 S.C.Chauhan, and R.Madhubala (2009).
Glyoxalase I gene deletion mutants of Leishmania donovani exhibit reduced methylglyoxal detoxification.
  PLoS One, 4, e6805.  
19101977 X.Wu, P.M.Flatt, H.Xu, and T.Mahmud (2009).
Biosynthetic Gene Cluster of Cetoniacytone A, an Unusual Aminocyclitol from the Endosymbiotic Bacterium Actinomyces sp. Lu 9419.
  Chembiochem, 10, 304-314.  
18695250 M.Kawatani, H.Okumura, K.Honda, N.Kanoh, M.Muroi, N.Dohmae, M.Takami, M.Kitagawa, Y.Futamura, M.Imoto, and H.Osada (2008).
The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I.
  Proc Natl Acad Sci U S A, 105, 11691-11696.
PDB code: 2za0
17664277 M.Deponte, N.Sturm, S.Mittler, M.Harner, H.Mack, and K.Becker (2007).
Allosteric coupling of two different functional active sites in monomeric Plasmodium falciparum glyoxalase I.
  J Biol Chem, 282, 28419-28430.  
16430697 A.Ariza, T.J.Vickers, N.Greig, K.A.Armour, M.J.Dixon, I.M.Eggleston, A.H.Fairlamb, and C.S.Bond (2006).
Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme.
  Mol Microbiol, 59, 1239-1248.
PDB code: 2c21
16844981 C.C.Chen, J.K.Hwang, and J.M.Yang (2006).
(PS)2: protein structure prediction server.
  Nucleic Acids Res, 34, W152-W157.  
  16511153 A.Ariza, T.J.Vickers, N.Greig, A.H.Fairlamb, and C.S.Bond (2005).
Crystallization and preliminary X-ray analysis of Leishmania major glyoxalase I.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 769-772.  
15548539 A.M.Neculai, D.Neculai, C.Griesinger, J.A.Vorholt, and S.Becker (2005).
A dynamic zinc redox switch.
  J Biol Chem, 280, 2826-2830.
PDB codes: 1x6m 1xa8
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.  
15329410 T.J.Vickers, N.Greig, and A.H.Fairlamb (2004).
A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in Leishmania major.
  Proc Natl Acad Sci U S A, 101, 13186-13191.  
12660999 R.G.Zhang, N.Duke, R.Laskowski, E.Evdokimova, T.Skarina, A.Edwards, A.Joachimiak, and A.Savchenko (2003).
Conserved protein YecM from Escherichia coli shows structural homology to metal-binding isomerases and oxygenases.
  Proteins, 51, 311-314.
PDB code: 1k4n
11470438 A.A.McCarthy, H.M.Baker, S.C.Shewry, M.L.Patchett, and E.N.Baker (2001).
Crystal structure of methylmalonyl-coenzyme A epimerase from P. shermanii: a novel enzymatic function on an ancient metal binding scaffold.
  Structure, 9, 637-646.
PDB codes: 1jc4 1jc5
11294624 G.Davidson, S.L.Clugston, J.F.Honek, and M.J.Maroney (2001).
An XAS investigation of product and inhibitor complexes of Ni-containing GlxI from Escherichia coli: mechanistic implications.
  Biochemistry, 40, 4569-4582.  
11395407 J.A.Gerlt, and P.C.Babbitt (2001).
Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies.
  Annu Rev Biochem, 70, 209-246.  
11223513 M.Jaskólski, M.Kozak, J.Lubkowski, G.Palm, and A.Wlodawer (2001).
Structures of two highly homologous bacterial L-asparaginases: a case of enantiomorphic space groups.
  Acta Crystallogr D Biol Crystallogr, 57, 369-377.
PDB codes: 1hfj 1hfk 1ho3
10913283 M.M.He, S.L.Clugston, J.F.Honek, and B.W.Matthews (2000).
Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation.
  Biochemistry, 39, 8719-8727.
PDB codes: 1f9z 1fa5 1fa6 1fa7 1fa8
11076500 R.N.Armstrong (2000).
Mechanistic diversity in a metalloenzyme superfamily.
  Biochemistry, 39, 13625-13632.  
10508780 A.D.Cameron, M.Ridderström, B.Olin, and B.Mannervik (1999).
Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue.
  Structure, 7, 1067-1078.
PDB codes: 1qh3 1qh5
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.