2OWZ: R-state, Citrate And Fru-6-p-bound Escherichia Coli Fructose-1,6- Bisphosphatase

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.
PDB ID: 2OWZDownload
MMDB ID: 44820
PDB Deposition Date: 2007/2/17
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.18  Å
Source Organism:
Similar Structures:
Biological Unit for 2OWZ: tetrameric; determined by author and by software (PQS)
Molecular Components in 2OWZ
Label Count Molecule
Proteins (4 molecules)
Fructose-1,6-bisphosphatase(Gene symbol: fbp)
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB