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2qvv
From Proteopedia
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Porcine Liver Fructose-1,6-bisphosphatase cocrystallized with Fru-2,6-P2 and Zn2+, I(T)-state
Overview
Fructose-1,6-bisphosphatase (FBPase) operates at a control point in, mammalian gluconeogenesis, being inhibited synergistically by fructose, 2,6-bisphosphate (Fru-2,6-P(2)) and AMP. AMP and Fru-2,6-P(2) bind to, allosteric and active sites, respectively, but the mechanism responsible, for AMP/Fru-2,6-P(2) synergy is unclear. Demonstrated here for the first, time is a global conformational change in porcine FBPase induced by, Fru-2,6-P(2) in the absence of AMP. The Fru-2,6-P(2) complex exhibits a, subunit-pair rotation of 13 degrees from the R-state (compared to the 15, degrees rotation of the T-state AMP complex) with active-site loops in the, disengaged conformation. A three-state thermodynamic model in which, Fru-2,6-P(2) drives a conformational change to a T-like intermediate state, can account for AMP/Fru-2,6-P(2) synergism in mammalian FBPases. AMP and, Fru-2,6-P(2) are not synergistic inhibitors of the Type I FBPase from, Escherichia coli, and consistent with that model, the complex of E. coli, FBPase with Fru-2,6-P(2) remains in the R-state with dynamic loops in the, engaged conformation. Evidently in porcine FBPase, the actions of AMP at, the allosteric site and Fru-2,6-P(2) at the active site displace engaged, dynamic loops by distinct mechanisms, resulting in similar quaternary, end-states. Conceivably, Type I FBPases from all eukaryotes may undergo, similar global conformational changes in response to Fru-2,6-P(2), ligation.
About this Structure
2QVV is a Single protein structure of sequence from Sus scrofa with , and as ligands. Active as Fructose-bisphosphatase, with EC number 3.1.3.11 Full crystallographic information is available from OCA.
Reference
Structures of mammalian and bacterial fructose-1,6-bisphosphatase reveal the basis for synergism in AMP/fructose 2,6-bisphosphate inhibition., Hines JK, Chen X, Nix JC, Fromm HJ, Honzatko RB, J Biol Chem. 2007 Oct 12;. PMID:17933867
Page seeded by OCA on Wed Jan 23 11:03:47 2008
