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PDBsum entry 1fa7

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protein metals Protein-protein interface(s) links
Lyase PDB id
1fa7
Jmol
Contents
Protein chains
128 a.a. *
Metals
_CD ×2
Waters ×259
* Residue conservation analysis
PDB id:
1fa7
Name: Lyase
Title: Crystal structure of cd(ii)-bound glyoxalase i of escherichia coli
Structure: Glyoxalase i. Chain: a, b. Synonym: lactoylglutathione lyase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.183     R-free:   0.281
Authors: M.M.He,S.L.Clugston,J.F.Honek,B.W.Matthews
Key ref:
M.M.He et al. (2000). Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation. Biochemistry, 39, 8719-8727. PubMed id: 10913283 DOI: 10.1021/bi000856g
Date:
12-Jul-00     Release date:   20-Sep-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0AC81  (LGUL_ECOLI) -  Lactoylglutathione lyase
Seq:
Struc:
135 a.a.
128 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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
= glutathione
+ methylglyoxal
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     methylglyoxal catabolic process to D-lactate   1 term 
  Biochemical function     protein binding     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi000856g Biochemistry 39:8719-8727 (2000)
PubMed id: 10913283  
 
 
Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation.
M.M.He, S.L.Clugston, J.F.Honek, B.W.Matthews.
 
  ABSTRACT  
 
The metalloenzyme glyoxalase I (GlxI) converts the nonenzymatically produced hemimercaptal of cytotoxic methylglyoxal and glutathione to nontoxic S-D-lactoylglutathione. Human GlxI, for which the structure is known, is active in the presence of Zn(2+). Unexpectedly, the Escherichia coli enzyme is inactive in the presence of Zn(2+) and is maximally active with Ni(2+). To understand this difference in metal activation and also to obtain a representative of the bacterial enzymes, the structure of E. coli Ni(2+)-GlxI has been determined. Structures have also been determined for the apo enzyme as well as complexes with Co(2+), Cd(2+), and Zn(2+). It is found that each of the protein-metal complexes that is catalytically active has octahedral geometry. This includes the complexes of the E. coli enzyme with Ni(2+), Co(2+), and Cd(2+), as well as the structures reported for the human Zn(2+) enzyme. Conversely, the complex of the E. coli enzyme with Zn(2+) has trigonal bipyramidal coordination and is inactive. This mode of coordination includes four protein ligands plus a single water molecule. In contrast, the coordination in the active forms of the enzyme includes two water molecules bound to the metal ion, suggesting that this may be a key feature of the catalytic mechanism. A comparison of the human and E. coli enzymes suggests that there are differences between the active sites that might be exploited for therapeutic use.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21310258 U.Suttisansanee, and J.F.Honek (2011).
Bacterial glyoxalase enzymes.
  Semin Cell Dev Biol, 22, 285-292.  
20333421 K.C.Ryan, O.E.Johnson, D.E.Cabelli, T.C.Brunold, and M.J.Maroney (2010).
Nickel superoxide dismutase: structural and functional roles of Cys2 and Cys6.
  J Biol Inorg Chem, 15, 795-807.  
19731367 L.Shi, P.Gao, X.X.Yan, and D.C.Liang (2009).
Crystal structure of a putative methylmalonyl-coenzyme a epimerase from Thermoanaerobacter tengcongensis at 2.0 A resolution.
  Proteins, 77, 994-999.
PDB code: 3gm5
  19319934 M.D.Suits, J.Lang, G.P.Pal, M.Couture, and Z.Jia (2009).
Structure and heme binding properties of Escherichia coli O157:H7 ChuX.
  Protein Sci, 18, 825-838.
PDB code: 2ovi
19710909 S.C.Chauhan, and R.Madhubala (2009).
Glyoxalase I gene deletion mutants of Leishmania donovani exhibit reduced methylglyoxal detoxification.
  PLoS One, 4, e6805.  
19363030 S.W.Ragsdale (2009).
Nickel-based Enzyme Systems.
  J Biol Chem, 284, 18571-18575.  
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.  
  18533363 N.Sukdeo, and J.F.Honek (2008).
Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal.
  Drug Metabol Drug Interact, 23, 29-50.  
  18533364 S.K.Yadav, S.L.Singla-Pareek, and S.K.Sopory (2008).
An overview on the role of methylglyoxal and glyoxalases in plants.
  Drug Metabol Drug Interact, 23, 51-68.  
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.  
16159764 J.L.Rowe, G.L.Starnes, and P.T.Chivers (2005).
Complex transcriptional control links NikABCDE-dependent nickel transport with hydrogenase expression in Escherichia coli.
  J Bacteriol, 187, 6317-6323.  
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.  
12829270 S.B.Mulrooney, and R.P.Hausinger (2003).
Nickel uptake and utilization by microorganisms.
  FEMS Microbiol Rev, 27, 239-261.  
12163508 J.S.Cavet, W.Meng, M.A.Pennella, R.J.Appelhoff, D.P.Giedroc, and N.J.Robinson (2002).
A nickel-cobalt-sensing ArsR-SmtB family repressor. Contributions of cytosol and effector binding sites to metal selectivity.
  J Biol Chem, 277, 38441-38448.  
  12426116 P.E.Carrington, F.Al-Mjeni, M.A.Zoroddu, M.Costa, and M.J.Maroney (2002).
Use of XAS for the elucidation of metal structure and function: applications to nickel biochemistry, molecular toxicology, and carcinogenesis.
  Environ Health Perspect, 110, 705-708.  
12121648 T.W.Martin, Z.Dauter, Y.Devedjiev, P.Sheffield, F.Jelen, M.He, D.H.Sherman, J.Otlewski, Z.S.Derewenda, and U.Derewenda (2002).
Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein.
  Structure, 10, 933-942.
PDB codes: 1kll 1kmz
12021428 Y.Liu, and D.Eisenberg (2002).
3D domain swapping: as domains continue to swap.
  Protein Sci, 11, 1285-1299.  
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.  
11076500 R.N.Armstrong (2000).
Mechanistic diversity in a metalloenzyme superfamily.
  Biochemistry, 39, 13625-13632.  
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.