2OWZ

R-state, citrate and Fru-6-P-bound Escherichia coli fructose-1,6-bisphosphatase

Summary for 2OWZ

• Entry DOI: 10.2210/pdb2owz/pdb
• Related: 2GQ1 2OX3
• Descriptor: Fructose-1,6-bisphosphatase, 6-O-phosphono-beta-D-fructofuranose, CITRIC ACID, ... (4 entities in total)
• Functional Keywords: glycolysis, gluconeogenesis, bacteria, carbohydrate metabolism, diabetes, protein-protein interactions, proteobacteria, gram-negative, protein crystallography, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 37613.49

Authors

Hines, J.K.,Fromm, H.J.,Honzatko, R.B. (deposition date: 2007-02-17, release date: 2007-03-06, Last modification date: 2024-11-06)

Primary citation

Hines, J.K.,Fromm, H.J.,Honzatko, R.B.
Structures of activated fructose-1,6-bisphosphatase from Escherichia coli. Coordinate regulation of bacterial metabolism and the conservation of the R-state.
J.Biol.Chem., 282:11696-11704, 2007

PubMed Abstract: The enteric bacterium Escherichia coli requires fructose-1,6-bisphosphatase (FBPase) for growth on gluconeogenic carbon sources. Constitutive expression of FBPase and fructose-6-phosphate-1-kinase coupled with the absence of futile cycling implies an undetermined mechanism of coordinate regulation involving both enzymes. Tricarboxylic acids and phosphorylated three-carbon carboxylic acids, all intermediates of glycolysis and the tricarboxylic acid cycle, are shown here to activate E. coli FBPase. The two most potent activators, phosphoenolpyruvate and citrate, bind to the sulfate anion site, revealed previously in the first crystal structure of the E. coli enzyme. Tetramers ligated with either phosphoenolpyruvate or citrate, in contrast to the sulfate-bound structure, are in the canonical R-state of porcine FBPase but nevertheless retain sterically blocked AMP pockets. At physiologically relevant concentrations, phosphoenolpyruvate and citrate stabilize an active tetramer over a less active enzyme form of mass comparable with that of a dimer. The above implies the conservation of the R-state through evolution. FBPases of heterotrophic organisms of distantly related phylogenetic groups retain residues of the allosteric activator site and in those instances where data are available exhibit activation by phosphoenolpyruvate. Findings here unify disparate observations regarding bacterial FBPases, implicating a mechanism of feed-forward activation in bacterial central metabolism.

PubMed: 17314096
DOI: 10.1074/jbc.M611104200

Experimental method

X-RAY DIFFRACTION (2.18 Å)