1zai
From Proteopedia
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|PDB= 1zai |SIZE=350|CAPTION= <scene name='initialview01'>1zai</scene>, resolution 1.76Å | |PDB= 1zai |SIZE=350|CAPTION= <scene name='initialview01'>1zai</scene>, resolution 1.76Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=2FP:1,6-FRUCTOSE DIPHOSPHATE (LINEAR FORM)'>2FP</scene> | + | |LIGAND= <scene name='pdbligand=2FP:1,6-FRUCTOSE+DIPHOSPHATE+(LINEAR+FORM)'>2FP</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Fructose-bisphosphate_aldolase Fructose-bisphosphate aldolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.2.13 4.1.2.13] </span> |
|GENE= ALDOA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | |GENE= ALDOA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1zah|1ZAH]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zai OCA], [http://www.ebi.ac.uk/pdbsum/1zai PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zai RCSB]</span> | ||
}} | }} | ||
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[[Category: St-Jean, M.]] | [[Category: St-Jean, M.]] | ||
[[Category: Sygusch, J.]] | [[Category: Sygusch, J.]] | ||
| - | [[Category: 2FP]] | ||
[[Category: aldolase]] | [[Category: aldolase]] | ||
[[Category: schiff base intermediate]] | [[Category: schiff base intermediate]] | ||
[[Category: substrate]] | [[Category: substrate]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:33:08 2008'' |
Revision as of 22:33, 30 March 2008
| |||||||
| , resolution 1.76Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ALDOA (Oryctolagus cuniculus) | ||||||
| Activity: | Fructose-bisphosphate aldolase, with EC number 4.1.2.13 | ||||||
| Related: | 1ZAH
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Fructose-1,6-bisphosphate Schiff base intermediate in FBP aldolase from rabbit muscle
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
1ZAI 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
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