2QVV

Porcine Liver Fructose-1,6-bisphosphatase cocrystallized with Fru-2,6-P2 and Zn2+, I(T)-state

Summary for 2QVV

• Entry DOI: 10.2210/pdb2qvv/pdb
• Related: 1CNQ 1EYK 1Q9D 2OX3 2QVR 2QVU
• Descriptor: Fructose-1,6-bisphosphatase 1, 2,6-di-O-phosphono-beta-D-fructofuranose, ZINC ION, ... (5 entities in total)
• Functional Keywords: homotetramer; sugar phosphatase fold, hydrolase
• Biological source: Sus scrofa (pig)
• Total number of polymer chains: 2
• Total formula weight: 74383.41

Authors

Hines, J.K.,Chen, X.,Nix, J.C.,Fromm, H.J.,Honzatko, R.B. (deposition date: 2007-08-08, release date: 2007-10-23, Last modification date: 2023-08-30)

Primary citation

Hines, J.K.,Chen, X.,Nix, J.C.,Fromm, H.J.,Honzatko, R.B.
Structures of mammalian and bacterial fructose-1,6-bisphosphatase reveal the basis for synergism in AMP/fructose 2,6-bisphosphate inhibition
J.Biol.Chem., 282:36121-36131, 2007

PubMed Abstract: 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 with 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.

PubMed: 17933867
DOI: 10.1074/jbc.M707302200

Experimental method

X-RAY DIFFRACTION (2.03 Å)