1zal: Difference between revisions
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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== | ||
<StructureSection load='1zal' size='340' side='right' caption='[[1zal]], [[Resolution|resolution]] 1.89Å' scene=''> | <StructureSection load='1zal' size='340' side='right' caption='[[1zal]], [[Resolution|resolution]] 1.89Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALDOA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALDOA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zal OCA], [http://pdbe.org/1zal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zal RCSB], [http://www.ebi.ac.uk/pdbsum/1zal PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zal OCA], [http://pdbe.org/1zal PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zal RCSB], [http://www.ebi.ac.uk/pdbsum/1zal PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zal ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 1zal" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1zal" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 13:36, 12 October 2017
Fructose-1,6-bisphosphate aldolase from rabbit muscle in complex with partially disordered tagatose-1,6-bisphosphate, a weak competitive inhibitorFructose-1,6-bisphosphate aldolase from rabbit muscle in complex with partially disordered tagatose-1,6-bisphosphate, a weak competitive inhibitor
Structural highlights
Function[ALDOA_RABIT] Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein.[1] 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 PubMedCrystal 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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