PDBsum entry 1fa7

Lyase

PDB id: 1fa7

Contents

Protein chains

128 a.a. *

Metals

_CD ×2

Waters ×259

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Determination of the structure of escherichia coli glyoxalase i suggests a structural basis for differential metal activation.
• Authors: M.M.He, S.L.Clugston, J.F.Honek, B.W.Matthews.
• Ref.: Biochemistry, 2000, 39, 8719-8727. [DOI no: 10.1021/bi000856g]
• PubMed id: 10913283

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.