1zal
From Proteopedia
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Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with partially disordered tagatose-1,6-bisphosphate, a weak competitive inhibitor
Overview
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.
About this Structure
1ZAL is a Single protein structure of sequence from Oryctolagus cuniculus with PO4 as ligand. Active as Fructose-bisphosphate aldolase, with EC number 4.1.2.13 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Wed Nov 21 07:20:50 2007
