1FA5

CRYSTAL STRUCTURE OF THE ZN(II)-BOUND GLYOXALASE I OF ESCHERICHIA COLI

Summary for 1FA5

• Entry DOI: 10.2210/pdb1fa5/pdb
• Related: 1F9Z 1FA6 1FA7 1FA8 1fro
• Descriptor: GLYOXALASE I, ZINC ION (3 entities in total)
• Functional Keywords: beta-alpha-beta-beta-beta motif, homodimer, zn(ii)-bound, lyase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 30004.45

Authors

He, M.M.,Clugston, S.L.,Honek, J.F.,Matthews, B.W. (deposition date: 2000-07-12, release date: 2000-09-20, Last modification date: 2024-02-07)

Primary citation

He, M.M.,Clugston, S.L.,Honek, J.F.,Matthews, B.W.
Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation.
Biochemistry, 39:8719-8727, 2000

PubMed 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.

PubMed: 10913283
DOI: 10.1021/bi000856g

Experimental method

X-RAY DIFFRACTION (1.8 Å)