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| | ==Crystal structure of MurD ligase in complex with D-Glu containing sulfonamide inhibitor== | | ==Crystal structure of MurD ligase in complex with D-Glu containing sulfonamide inhibitor== |
| - | <StructureSection load='2vtd' size='340' side='right' caption='[[2vtd]], [[Resolution|resolution]] 1.94Å' scene=''> | + | <StructureSection load='2vtd' size='340' side='right'caption='[[2vtd]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vtd]] is a 1 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=2VTD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VTD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vtd]] is a 1 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=2VTD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VTD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LKM:N-({6-[(4-CYANO-2-FLUOROBENZYL)OXY]NAPHTHALEN-2-YL}SULFONYL)-D-GLUTAMIC+ACID'>LKM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.94Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=LKM:N-({6-[(4-CYANO-2-FLUOROBENZYL)OXY]NAPHTHALEN-2-YL}SULFONYL)-D-GLUTAMIC+ACID'>LKM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2uuo|2uuo]], [[2jfg|2jfg]], [[4uag|4uag]], [[1uag|1uag]], [[2jfh|2jfh]], [[2uag|2uag]], [[3uag|3uag]], [[2uup|2uup]], [[1e0d|1e0d]], [[1eeh|1eeh]], [[2jff|2jff]], [[2vte|2vte]]</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=2vtd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vtd OCA], [https://pdbe.org/2vtd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vtd RCSB], [https://www.ebi.ac.uk/pdbsum/2vtd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vtd 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/UDP-N-acetylmuramoyl-L-alanine--D-glutamate_ligase UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.9 6.3.2.9] </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=2vtd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vtd OCA], [http://pdbe.org/2vtd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vtd RCSB], [http://www.ebi.ac.uk/pdbsum/2vtd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vtd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MURD_ECOLI MURD_ECOLI]] Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA).[HAMAP-Rule:MF_00639] | + | [https://www.uniprot.org/uniprot/MURD_ECOLI MURD_ECOLI] Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA).[HAMAP-Rule:MF_00639] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2vtd" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2vtd" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Mur ligase|Mur ligase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase]] | + | [[Category: Large Structures]] |
| - | [[Category: Blanot, D]] | + | [[Category: Blanot D]] |
| - | [[Category: Contreras-Martel, C]] | + | [[Category: Contreras-Martel C]] |
| - | [[Category: Dessen, A]] | + | [[Category: Dessen A]] |
| - | [[Category: Gobec, S]] | + | [[Category: Gobec S]] |
| - | [[Category: Humljan, J]] | + | [[Category: Humljan J]] |
| - | [[Category: Kotnik, M]] | + | [[Category: Kotnik M]] |
| - | [[Category: Solmajer, T]] | + | [[Category: Solmajer T]] |
| - | [[Category: Urleb, U]] | + | [[Category: Urleb U]] |
| - | [[Category: Atp-binding]]
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| - | [[Category: Cell cycle]]
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| - | [[Category: Cell division]]
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| - | [[Category: Cell shape]]
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| - | [[Category: Cell wall biogenesis/degradation]]
| + | |
| - | [[Category: Cytoplasm]]
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| - | [[Category: Ligase]]
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| - | [[Category: Murd ligase]]
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| - | [[Category: Murd-inhibitor complex]]
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| - | [[Category: Nucleotide-binding]]
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| - | [[Category: Peptidoglycan synthesis]]
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| - | [[Category: Sulfonamide inhibitor]]
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| Structural highlights
Function
MURD_ECOLI Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA).[HAMAP-Rule:MF_00639]
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
Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP- N-acetylmuramoyl- l-alanine: d-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of d-glutamic acid ( d-Glu) to the cytoplasmic intermediate UDP- N-acetylmuramoyl- l-alanine (UMA). Because of the high binding affinity of d-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted d-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships. The substituted naphthalene- N-sulfonyl- d-Glu inhibitors, which were synthesized as potential transition-state analogues, displayed IC 50 values ranging from 80 to 600 muM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.
Novel Naphthalene-N-sulfonyl-d-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme.,Humljan J, Kotnik M, Contreras-Martel C, Blanot D, Urleb U, Dessen A, Solmajer T, Gobec S J Med Chem. 2008 Nov 13. PMID:19007109[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Humljan J, Kotnik M, Contreras-Martel C, Blanot D, Urleb U, Dessen A, Solmajer T, Gobec S. Novel Naphthalene-N-sulfonyl-d-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme. J Med Chem. 2008 Nov 13. PMID:19007109 doi:10.1021/jm800762u
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