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| | ==Crystal Structure of the C123S 2-Methylisocitrate Lyase Mutant from Escherichia coli in complex with the inhibitor isocitrate== | | ==Crystal Structure of the C123S 2-Methylisocitrate Lyase Mutant from Escherichia coli in complex with the inhibitor isocitrate== |
| - | <StructureSection load='1xg4' size='340' side='right' caption='[[1xg4]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='1xg4' size='340' side='right'caption='[[1xg4]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xg4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XG4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xg4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XG4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xg3|1xg3]], [[1oqf|1oqf]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ICT:ISOCITRIC+ACID'>ICT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">prpB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=1xg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xg4 OCA], [https://pdbe.org/1xg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xg4 RCSB], [https://www.ebi.ac.uk/pdbsum/1xg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xg4 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/Methylisocitrate_lyase Methylisocitrate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.30 4.1.3.30] </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=1xg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xg4 OCA], [http://pdbe.org/1xg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xg4 RCSB], [http://www.ebi.ac.uk/pdbsum/1xg4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xg4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRPB_ECOLI PRPB_ECOLI]] Catalyzes the formation of pyruvate and succinate from 2-methylisocitrate.<ref>PMID:11422389</ref> <ref>PMID:15723538</ref> | + | [https://www.uniprot.org/uniprot/PRPB_ECOLI PRPB_ECOLI] Catalyzes the formation of pyruvate and succinate from 2-methylisocitrate.<ref>PMID:11422389</ref> <ref>PMID:15723538</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: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Methylisocitrate lyase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dunaway-Mariano, D]] | + | [[Category: Dunaway-Mariano D]] |
| - | [[Category: Han, Y]] | + | [[Category: Han Y]] |
| - | [[Category: Herzberg, O]] | + | [[Category: Herzberg O]] |
| - | [[Category: Liu, S]] | + | [[Category: Liu S]] |
| - | [[Category: Lu, Z]] | + | [[Category: Lu Z]] |
| - | [[Category: Melamud, E]] | + | [[Category: Melamud E]] |
| - | [[Category: 2-methylisocitrate lyase-inhibitor complex]]
| + | |
| - | [[Category: Isocitrate]]
| + | |
| - | [[Category: Isocitrate lyase superfamily]]
| + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
PRPB_ECOLI Catalyzes the formation of pyruvate and succinate from 2-methylisocitrate.[1] [2]
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
Two crystal structures of the C123S mutant of 2-methylisocitrate lyase have been determined, one with the bound reaction products, Mg(2+)-pyruvate and succinate, and the second with a bound Mg(2+)-(2R,3S)-isocitrate inhibitor. Comparison with the structure of the wild-type enzyme in the unbound state reveals that the enzyme undergoes a conformational transition that sequesters the ligand from solvent, as previously observed for two other enzyme superfamily members, isocitrate lyase and phosphoenolpyruvate mutase. The binding modes reveal the determinants of substrate specificity and stereoselectivity, and the stringent specificity is verified in solution using various potential substrates. A model of bound 2-methylisocitrate has been developed based on the experimentally determined structures. We propose a catalytic mechanism involving an alpha-carboxy-carbanion intermediate/transition state, which is consistent with previous stereochemical experiments showing inversion of configuration at the C(3) of 2-methylisocitrate. Structure-based sequence analysis and phylogenic tree construction reveal determinants of substrate specificity, highlight nodes of divergence of families, and predict enzyme families with new functions.
Crystal structures of 2-methylisocitrate lyase in complex with product and with isocitrate inhibitor provide insight into lyase substrate specificity, catalysis and evolution.,Liu S, Lu Z, Han Y, Melamud E, Dunaway-Mariano D, Herzberg O Biochemistry. 2005 Mar 1;44(8):2949-62. PMID:15723538[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Brock M, Darley D, Textor S, Buckel W. 2-Methylisocitrate lyases from the bacterium Escherichia coli and the filamentous fungus Aspergillus nidulans: characterization and comparison of both enzymes. Eur J Biochem. 2001 Jun;268(12):3577-86. PMID:11422389
- ↑ Liu S, Lu Z, Han Y, Melamud E, Dunaway-Mariano D, Herzberg O. Crystal structures of 2-methylisocitrate lyase in complex with product and with isocitrate inhibitor provide insight into lyase substrate specificity, catalysis and evolution. Biochemistry. 2005 Mar 1;44(8):2949-62. PMID:15723538 doi:http://dx.doi.org/10.1021/bi0479712
- ↑ Liu S, Lu Z, Han Y, Melamud E, Dunaway-Mariano D, Herzberg O. Crystal structures of 2-methylisocitrate lyase in complex with product and with isocitrate inhibitor provide insight into lyase substrate specificity, catalysis and evolution. Biochemistry. 2005 Mar 1;44(8):2949-62. PMID:15723538 doi:http://dx.doi.org/10.1021/bi0479712
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