2gc3
The crystal structure of phosphoglucose isomerase from Pyrococcus furiosus in complex with mannose 6-phosphate and zinc
|
OverviewOverview
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.
About this StructureAbout this Structure
2GC3 is a Single protein structure of sequence from Pyrococcus furiosus with ZN and M6P as ligands. Active as Glucose-6-phosphate isomerase, with EC number 5.3.1.9 Full crystallographic information is available from OCA.
ReferenceReference
Evidence supporting a cis-enediol-based mechanism for Pyrococcus furiosus phosphoglucose isomerase., Berrisford JM, Hounslow AM, Akerboom J, Hagen WR, Brouns SJ, van der Oost J, Murray IA, Michael Blackburn G, Waltho JP, Rice DW, Baker PJ, J Mol Biol. 2006 May 19;358(5):1353-66. Epub 2006 Mar 24. PMID:16580686
Page seeded by OCA on Wed Nov 21 11:06:33 2007