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| | <StructureSection load='5vjd' size='340' side='right'caption='[[5vjd]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='5vjd' size='340' side='right'caption='[[5vjd]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vjd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VJD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VJD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vjd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VJD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=13P:1,3-DIHYDROXYACETONEPHOSPHATE'>13P</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.701Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vjf|5vjf]], [[5vje|5vje]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=13P:1,3-DIHYDROXYACETONEPHOSPHATE'>13P</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fbaA, fba, fda, b2925, JW2892 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=5vjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vjd OCA], [https://pdbe.org/5vjd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vjd RCSB], [https://www.ebi.ac.uk/pdbsum/5vjd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vjd 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vjd OCA], [http://pdbe.org/5vjd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vjd RCSB], [http://www.ebi.ac.uk/pdbsum/5vjd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vjd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ALF_ECOLI ALF_ECOLI]] Catalyzes the aldol condensation of dihydroxyacetone phosphate (DHAP or glycerone-phosphate) with glyceraldehyde 3-phosphate (G3P) to form fructose 1,6-bisphosphate (FBP) in gluconeogenesis and the reverse reaction in glycolysis.<ref>PMID:10712619</ref> | + | [https://www.uniprot.org/uniprot/ALF_ECOLI ALF_ECOLI] Catalyzes the aldol condensation of dihydroxyacetone phosphate (DHAP or glycerone-phosphate) with glyceraldehyde 3-phosphate (G3P) to form fructose 1,6-bisphosphate (FBP) in gluconeogenesis and the reverse reaction in glycolysis.<ref>PMID:10712619</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Fructose-bisphosphate aldolase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Coincon, M]] | + | [[Category: Coincon M]] |
| - | [[Category: Sygusch, J]] | + | [[Category: Sygusch J]] |
| - | [[Category: Glycolysis]]
| + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
ALF_ECOLI Catalyzes the aldol condensation of dihydroxyacetone phosphate (DHAP or glycerone-phosphate) with glyceraldehyde 3-phosphate (G3P) to form fructose 1,6-bisphosphate (FBP) in gluconeogenesis and the reverse reaction in glycolysis.[1]
Publication Abstract from PubMed
Crystal structures of two bacterial metal (Zn) dependent D-fructose 1,6-bisphosphate (FBP) aldolases in complex with substrate, analogues, and triose-P reaction products were determined to 1.5-2.0 A resolution. The ligand complexes cryotrapped in native or mutant H. pylori aldolase crystals enabled a novel mechanistic description of FBP C3-C4 bond cleavage. The reaction mechanism uses active site remodelling during the catalytic cycle implicating relocation of the Zn cofactor that is mediated by conformational changes of active site loops. Substrate binding initiates conformational changes, triggered upon P1-phosphate binding, which liberates the Zn chelating His180, allowing it to act as a general base for the proton abstraction at the FBP C4-hydroxyl group. A second zinc chelating His83 hydrogen bonds the substrate C4- hydroxyl group and assists cleavage by stabilizing the developing negative charge during proton abstraction. Cleavage is concerted with relocation of the metal cofactor from an interior to a surface exposed site, thereby stabilizing the nascent enediolate form. Conserved residue Glu142 is essential for protonation of the enediolate form, prior to product release. A D-tagatose 1,6-bisphosphate enzymatic complex reveals how His180 mediated proton abstraction controls stereospecificity of the cleavage reaction. Recognition and discrimination of the reaction products, dihydroxyacetone-P and D-glyceraldehyde-3-P, occurs via charged hydrogen bonds between hydroxyl groups of the triose-Ps and conserved residues, Asp82 and Asp255, respectively, and are crucial aspects of the enzyme's role in gluconeogenesis. Conformational changes in mobile loops beta5-alpha7 and beta6-alpha8 (containing catalytic residues Glu142 and His180, respectively) drive active site remodelling enabling the relocation of the metal cofactor.
Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6-bisphosphate aldolases.,Jacques B, Coincon M, Sygusch J J Biol Chem. 2018 Mar 28. pii: RA117.001098. doi: 10.1074/jbc.RA117.001098. PMID:29593097[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zgiby SM, Thomson GJ, Qamar S, Berry A. Exploring substrate binding and discrimination in fructose1, 6-bisphosphate and tagatose 1,6-bisphosphate aldolases. Eur J Biochem. 2000 Mar;267(6):1858-68. PMID:10712619
- ↑ Jacques B, Coincon M, Sygusch J. Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6-bisphosphate aldolases. J Biol Chem. 2018 Mar 28. pii: RA117.001098. doi: 10.1074/jbc.RA117.001098. PMID:29593097 doi:http://dx.doi.org/10.1074/jbc.RA117.001098
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