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| | <StructureSection load='1zaj' size='340' side='right'caption='[[1zaj]], [[Resolution|resolution]] 1.89Å' scene=''> | | <StructureSection load='1zaj' size='340' side='right'caption='[[1zaj]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zaj]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZAJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1ZAJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zaj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZAJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZAJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M2P:D-MANNITOL-1,6-DIPHOSPHATE'>M2P</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.89Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1zah|1zah]], [[1zai|1zai]], [[1zal|1zal]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M2P:D-MANNITOL-1,6-DIPHOSPHATE'>M2P</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zaj OCA], [https://pdbe.org/1zaj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zaj RCSB], [https://www.ebi.ac.uk/pdbsum/1zaj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zaj ProSAT]</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://proteopedia.org/fgij/fg.htm?mol=1zaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zaj OCA], [http://pdbe.org/1zaj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zaj RCSB], [http://www.ebi.ac.uk/pdbsum/1zaj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zaj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ALDOA_RABIT ALDOA_RABIT]] Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein.<ref>PMID:17329259</ref> | + | [https://www.uniprot.org/uniprot/ALDOA_RABIT ALDOA_RABIT] Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein.<ref>PMID:17329259</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: European rabbit]] | |
| - | [[Category: Fructose-bisphosphate aldolase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lafrance-Vanasse, J]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Liotard, B]] | + | [[Category: Lafrance-Vanasse J]] |
| - | [[Category: St-Jean, M]] | + | [[Category: Liotard B]] |
| - | [[Category: Sygusch, J]] | + | [[Category: St-Jean M]] |
| - | [[Category: 6-bisphosphate]]
| + | [[Category: Sygusch J]] |
| - | [[Category: Aldolase]]
| + | |
| - | [[Category: Competitive inhibitor]]
| + | |
| - | [[Category: Hexitol-1]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Mannitol-1]]
| + | |
| - | [[Category: Non covalent complex]]
| + | |
| 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 PubMed
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.
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.
See Also
References
- ↑ St-Jean M, Izard T, Sygusch J. A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with Wiskott-Aldrich syndrome protein. J Biol Chem. 2007 May 11;282(19):14309-15. Epub 2007 Feb 27. PMID:17329259 doi:10.1074/jbc.M611505200
- ↑ St-Jean M, Lafrance-Vanasse J, Liotard B, Sygusch J. High resolution reaction intermediates of rabbit muscle fructose-1,6-bisphosphate aldolase: substrate cleavage and induced fit. J Biol Chem. 2005 Jul 22;280(29):27262-70. Epub 2005 May 3. PMID:15870069 doi:10.1074/jbc.M502413200
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