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| | <StructureSection load='2fq6' size='340' side='right'caption='[[2fq6]], [[Resolution|resolution]] 1.78Å' scene=''> | | <StructureSection load='2fq6' size='340' side='right'caption='[[2fq6]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fq6]] is a 2 chain structure with sequence from [https://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=2FQ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FQ6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fq6]] is a 2 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=2FQ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FQ6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P3F:PHOSPHORIC+ACID+MONO-(5-HYDROXY-6-METHYL-4-{[2-(2-TRIFLUOROMETHYL-BENZOYLAMINO)-ACETYL]-HYDRAZONOMETHYL}-PYRIDIN-3-YLMETHYL)ESTER'>P3F</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]] 1.78Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">metC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P3F:PHOSPHORIC+ACID+MONO-(5-HYDROXY-6-METHYL-4-{[2-(2-TRIFLUOROMETHYL-BENZOYLAMINO)-ACETYL]-HYDRAZONOMETHYL}-PYRIDIN-3-YLMETHYL)ESTER'>P3F</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cystathionine_beta-lyase Cystathionine beta-lyase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.4.1.8 4.4.1.8] </span></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=2fq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fq6 OCA], [https://pdbe.org/2fq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fq6 RCSB], [https://www.ebi.ac.uk/pdbsum/2fq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fq6 ProSAT]</span></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=2fq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fq6 OCA], [https://pdbe.org/2fq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fq6 RCSB], [https://www.ebi.ac.uk/pdbsum/2fq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fq6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/METC_ECOLI METC_ECOLI] |
| | == 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: Cystathionine beta-lyase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Junop, M S]] | + | [[Category: Junop MS]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Plp cofactor covalently bound to p3f inhibitor]]
| + | |
| - | [[Category: Protein-inhibitor complex]]
| + | |
| Structural highlights
Function
METC_ECOLI
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
The biosynthesis of methionine is an attractive antibiotic target given its importance in protein and DNA metabolism and its absence in mammals. We have performed a high-throughput screen of the methionine biosynthesis enzyme cystathionine beta-lyase (CBL) against a library of 50 000 small molecules and have identified several compounds that inhibit CBL enzyme activity in vitro. These hit molecules were of two classes: those that blocked CBL activity with mixed steady-state inhibition and those that covalently interacted with the enzyme at the active site pyridoxal phosphate cofactor with slow-binding inhibition kinetics. We determined the crystal structure of one of the slow-binding inhibitors in complex with CBL and used this structure as a guide in the synthesis of a small, focused library of analogues, some of which had improved enzyme inhibition properties. These studies provide the first lead molecules for antimicrobial agents that target cystathionine beta-lyase in methionine biosynthesis.
Inhibitors of bacterial cystathionine beta-lyase: leads for new antimicrobial agents and probes of enzyme structure and function.,Ejim LJ, Blanchard JE, Koteva KP, Sumerfield R, Elowe NH, Chechetto JD, Brown ED, Junop MS, Wright GD J Med Chem. 2007 Feb 22;50(4):755-64. PMID:17300162[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ejim LJ, Blanchard JE, Koteva KP, Sumerfield R, Elowe NH, Chechetto JD, Brown ED, Junop MS, Wright GD. Inhibitors of bacterial cystathionine beta-lyase: leads for new antimicrobial agents and probes of enzyme structure and function. J Med Chem. 2007 Feb 22;50(4):755-64. PMID:17300162 doi:10.1021/jm061132r
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