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''' | '''Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with partially disordered tagatose-1,6-bisphosphate, a weak competitive inhibitor''' | ||
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[[Category: St-Jean, M.]] | [[Category: St-Jean, M.]] | ||
[[Category: Sygusch, J.]] | [[Category: Sygusch, J.]] | ||
| - | [[Category: | + | [[Category: Aldolase]] |
| - | [[Category: | + | [[Category: Non covalent complex]] |
| - | [[Category: | + | [[Category: Tagatose-1,6-bisphosphate]] |
| - | [[Category: | + | [[Category: Weak competitive inhibitor]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:23:35 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:23, 3 May 2008
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. 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 Sat May 3 17:23:35 2008
