1zaj

Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with mannitol-1,6-bisphosphate, a competitive inhibitorFructose-1,6-bisphosphate aldolase from rabbit muscle in complex with mannitol-1,6-bisphosphate, a competitive inhibitor

Structural highlights 1zaj is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.89Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ALDOA_RABIT Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Crystal structures were determined to 1.8 A resolution of the glycolytic enzyme fructose-1,6-bis(phosphate) aldolase trapped in complex with its substrate and a competitive inhibitor, mannitol-1,6-bis(phosphate). The enzyme substrate complex corresponded to the postulated Schiff base intermediate and has reaction geometry consistent with incipient C3-C4 bond cleavage catalyzed Glu-187, which is adjacent by to the Schiff base forming Lys-229. Atom arrangement about the cleaved bond in the reaction intermediate mimics a pericyclic transition state occurring in nonenzymatic aldol condensations. Lys-146 hydrogen-bonds the substrate C4 hydroxyl and assists substrate cleavage by stabilizing the developing negative charge on the C4 hydroxyl during proton abstraction. Mannitol-1,6-bis(phosphate) forms a noncovalent complex in the active site whose binding geometry mimics the covalent carbinolamine precursor. Glu-187 hydrogen-bonds the C2 hydroxyl of the inhibitor in the enzyme complex, substantiating a proton transfer role by Glu-187 in catalyzing the conversion of the carbinolamine intermediate to Schiff base. Modeling of the acyclic substrate configuration into the active site shows Glu-187, in acid form, hydrogen-bonding both substrate C2 carbonyl and C4 hydroxyl, thereby aligning the substrate ketose for nucleophilic attack by Lys-229. The multifunctional role of Glu-187 epitomizes a canonical mechanistic feature conserved in Schiff base-forming aldolases catalyzing carbohydrate metabolism. Trapping of tagatose-1,6-bis(phosphate), a diastereoisomer of fructose 1,6-bis(phosphate), displayed stereospecific discrimination and reduced ketohexose binding specificity. Each ligand induces homologous conformational changes in two adjacent alpha-helical regions that promote phosphate binding in the active site. High resolution reaction intermediates of rabbit muscle fructose-1,6-bisphosphate aldolase: substrate cleavage and induced fit.,St-Jean M, Lafrance-Vanasse J, Liotard B, Sygusch J J Biol Chem. 2005 Jul 22;280(29):27262-70. Epub 2005 May 3. PMID:15870069 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldolase 3D structures DNA polymerase 3D structures

spinqualitylabelsall models 1zaj, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image