1E59

E.coli cofactor-dependent phosphoglycerate mutase complexed with vanadate

Summary for 1E59

• Entry DOI: 10.2210/pdb1e59/pdb
• Related: 1E58
• Descriptor: PHOSPHOGLYCERATE MUTASE, TETRAMETAVANADATE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: inhibitor, vandate, glycolysis and gluconeogenesis, phosphoglycerate mutase, isomerase
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 1
• Total formula weight: 28912.41

Authors

Bond, C.S.,Hunter, W.N. (deposition date: 2000-07-19, release date: 2002-02-05, Last modification date: 2023-12-13)

Primary citation

Bond, C.S.,White, M.,Hunter, W.N.
Mechanistic Implications for Escherichia Coli Cofactor-Dependent Phosphoglycerate Mutase Based on the High-Resolution Crystal Structure of a Vanadate Complex.
J.Mol.Biol., 316:1071-, 2002

PubMed Abstract: The structure of Escherichia coli cofactor-dependent phosphoglycerate mutase (dPGM), complexed with the potent inhibitor vanadate, has been determined to a resolution of 1.30 A (R-factor 0.159; R-free 0.213). The inhibitor is present in the active site, principally as divanadate, but with evidence of additional vanadate moieties at either end, and representing a different binding mode to that observed in the structural homologue prostatic acid phosphatase. The analysis reveals the enzyme-ligand interactions involved in inhibition of the mutase activity by vanadate and identifies a water molecule, observed in the native E.coli dPGM structure which, once activated by vanadate, may dephosphorylate the active protein. Rather than reflecting the active conformation previously observed for E.coli dPGM, the inhibited protein's conformation resembles that of the inactive dephosphorylated Saccharomyces cerevisiae dPGM. The provision of a high-resolution structure of both active and inactive forms of dPGM from a single organism, in conjunction with computational modelling of substrate molecules in the active site provides insight into the binding of substrates and the specific interactions necessary for three different activities, mutase, synthase and phosphatase, within a single active site. The sequence similarity of E.coli and human dPGMs allows us to correlate structure with clinical pathology.

PubMed: 11884145
DOI: 10.1006/JMBI.2002.5418

Experimental method

X-RAY DIFFRACTION (1.3 Å)