2GC0

The crystal structure of phosphoglucose isomerase from Pyrococcus furiosus in complex with 5-phospho-D-arabinonohydroxamate and zinc

Summary for 2GC0

• Entry DOI: 10.2210/pdb2gc0/pdb
• Related: 1QXJ 1QXR 1QY4 1X7N 1X82 1X8E 2GC1 2GC2 2GC3
• Descriptor: Glucose-6-phosphate isomerase, ZINC ION, 5-PHOSPHO-D-ARABINOHYDROXAMIC ACID, ... (4 entities in total)
• Functional Keywords: cupin, phosphoglucose isomerase, 5-phospho-d-arabinonohydroxamate, isomerase
• Biological source: Pyrococcus furiosus
• Cellular location: Cytoplasm: P83194
• Total number of polymer chains: 2
• Total formula weight: 43409.61

Authors

Berrisford, J.M.,Rice, D.W.,Baker, P.J. (deposition date: 2006-03-13, release date: 2006-04-11, Last modification date: 2023-08-30)

Primary citation

Berrisford, J.M.,Hounslow, A.M.,Akerboom, J.,Hagen, W.R.,Brouns, S.J.,van der Oost, J.,Murray, I.A.,Michael Blackburn, G.,Waltho, J.P.,Rice, D.W.,Baker, P.J.
Evidence Supporting a cis-enediol-based Mechanism for Pyrococcus furiosus Phosphoglucose Isomerase
J.Mol.Biol., 358:1353-1366, 2006

PubMed Abstract: The enzymatic aldose ketose isomerisation of glucose and fructose sugars involves the transfer of a hydrogen between their C1 and C2 carbon atoms and, in principle, can proceed through either a direct hydride shift or via a cis-enediol intermediate. Pyrococcus furiosus phosphoglucose isomerase (PfPGI), an archaeal metalloenzyme, which catalyses the interconversion of glucose 6-phosphate and fructose 6-phosphate, has been suggested to operate via a hydride shift mechanism. In contrast, the structurally distinct PGIs of eukaryotic or bacterial origin are thought to catalyse isomerisation via a cis-enediol intermediate. We have shown by NMR that hydrogen exchange between substrate and solvent occurs during the reaction catalysed by PfPGI eliminating the possibility of a hydride-shift-based mechanism. In addition, kinetic measurements on this enzyme have shown that 5-phospho-d-arabinonohydroxamate, a stable analogue of the putative cis-enediol intermediate, is the most potent inhibitor of the enzyme yet discovered. Furthermore, determination and analysis of crystal structures of PfPGI with bound zinc and the substrate F6P, and with a number of competitive inhibitors, and EPR analysis of the coordination of the metal ion within PfPGI, have suggested that a cis-enediol intermediate-based mechanism is used by PfPGI with Glu97 acting as the catalytic base responsible for isomerisation.

PubMed: 16580686
DOI: 10.1016/j.jmb.2006.03.015

Experimental method

X-RAY DIFFRACTION (2 Å)