PDBsum entry 1fa5

Lyase

PDB id: 1fa5

Contents

Protein chains

128 a.a. *

Metals

_ZN ×2

Waters ×230

* Residue conservation analysis

PDB id:

1fa5

Name:

Lyase

Title:

Crystal structure of the zn(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:

1.80Å R-factor: 0.194 R-free: 0.260

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

Protein chains

P0AC81  (LGUL_ECOLI) -  Lactoylglutathione lyase from Escherichia coli (strain K12)

Seq: 135 a.a.

Struc: 128 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.4.4.1.5 - lactoylglutathione lyase.
• Reaction: (R)-S-lactoylglutathione = methylglyoxal + glutathione

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

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.