1zai: Difference between revisions
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[[Image:1zai.gif|left|200px]] | [[Image:1zai.gif|left|200px]] | ||
'''Fructose-1,6-bisphosphate Schiff base intermediate in FBP aldolase from rabbit muscle''' | {{Structure | ||
|PDB= 1zai |SIZE=350|CAPTION= <scene name='initialview01'>1zai</scene>, resolution 1.76Å | |||
|SITE= | |||
|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] | |||
|GENE= ALDOA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus]) | |||
}} | |||
'''Fructose-1,6-bisphosphate Schiff base intermediate in FBP aldolase from rabbit muscle''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1ZAI is a [ | 1ZAI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZAI OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15870069 15870069] | ||
[[Category: Fructose-bisphosphate aldolase]] | [[Category: Fructose-bisphosphate aldolase]] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
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[[Category: substrate]] | [[Category: substrate]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:33:12 2008'' | ||
Revision as of 16:33, 20 March 2008
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| , resolution 1.76Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ALDOA (Oryctolagus cuniculus) | ||||||
| Activity: | Fructose-bisphosphate aldolase, with EC number 4.1.2.13 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Fructose-1,6-bisphosphate Schiff base intermediate in FBP aldolase from rabbit muscle
OverviewOverview
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 StructureAbout this Structure
1ZAI is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
ReferenceReference
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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