2qvv
From Proteopedia
(New page: 200px<br /><applet load="2qvv" size="350" color="white" frame="true" align="right" spinBox="true" caption="2qvv, resolution 2.030Å" /> '''Porcine Liver Fruct...) |
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==Overview== | ==Overview== | ||
| - | Fructose-1,6-bisphosphatase (FBPase) operates at a control point in | + | 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. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==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 | + | 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 Dec 7;282(49):36121-31. Epub 2007 Oct 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17933867 17933867] |
[[Category: Fructose-bisphosphatase]] | [[Category: Fructose-bisphosphatase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Chen, X.]] | [[Category: Chen, X.]] | ||
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Hines, J | + | [[Category: Hines, J K.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
| - | [[Category: Nix, J | + | [[Category: Nix, J C.]] |
[[Category: FDP]] | [[Category: FDP]] | ||
[[Category: PO4]] | [[Category: PO4]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:42:42 2008'' |
Revision as of 16:42, 21 February 2008
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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 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.
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 Dec 7;282(49):36121-31. Epub 2007 Oct 12. PMID:17933867
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