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| | <StructureSection load='6nj0' size='340' side='right'caption='[[6nj0]], [[Resolution|resolution]] 1.83Å' scene=''> | | <StructureSection load='6nj0' size='340' side='right'caption='[[6nj0]], [[Resolution|resolution]] 1.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nj0]] is a 1 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=6NJ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NJ0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nj0]] is a 1 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=6NJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NJ0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KOY:5-O-{3-[3-(2-carboxyphenyl)-3-oxopropyl]phenyl}adenosine'>KOY</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]] 1.83Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">menE, b2260, JW2255 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KOY:5-O-{3-[3-(2-carboxyphenyl)-3-oxopropyl]phenyl}adenosine'>KOY</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/o-succinylbenzoate--CoA_ligase o-succinylbenzoate--CoA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.26 6.2.1.26] </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=6nj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nj0 OCA], [https://pdbe.org/6nj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nj0 RCSB], [https://www.ebi.ac.uk/pdbsum/6nj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nj0 ProSAT]</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=6nj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nj0 OCA], [http://pdbe.org/6nj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nj0 RCSB], [http://www.ebi.ac.uk/pdbsum/6nj0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nj0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MENE_ECOLI MENE_ECOLI]] Converts 2-succinylbenzoate (OSB) to 2-succinylbenzoyl-CoA (OSB-CoA).[HAMAP-Rule:MF_00731]<ref>PMID:8626063</ref> | + | [https://www.uniprot.org/uniprot/MENE_ECOLI MENE_ECOLI] Converts 2-succinylbenzoate (OSB) to 2-succinylbenzoyl-CoA (OSB-CoA).[HAMAP-Rule:MF_00731]<ref>PMID:8626063</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | N-Acyl sulfamoyladenosines (acyl-AMS) have been used extensively to inhibit adenylate-forming enzymes that are involved in a wide range of biological processes. These acyl-AMS inhibitors are nonhydrolyzable mimics of the cognate acyl adenylate intermediates that are bound tightly by adenylate-forming enzymes. However, the anionic acyl sulfamate moiety presents a pharmacological liability that may be detrimental to cell permeability and pharmacokinetic profiles. We have previously developed the acyl sulfamate OSB-AMS (1) as a potent inhibitor of the adenylate-forming enzyme MenE, an o-succinylbenzoate-CoA (OSB-CoA) synthetase that is required for bacterial menaquinone biosynthesis. Herein, we report the use of computational docking to develop novel, non-acyl sulfamate inhibitors of MenE. A m-phenyl ether-linked analogue (5) was found to be the most potent inhibitor (IC50 = 8 muM; Kd = 244 nM), and its X-ray co-crystal structure was determined to characterize its binding mode in comparison to the computational prediction. This work provides a framework for the development of potent non-acyl sulfamate inhibitors of other adenylate-forming enzymes in the future.
| + | |
| - | | + | |
| - | Structure-Based Design, Synthesis, and Biological Evaluation of Non-Acyl Sulfamate Inhibitors of the Adenylate-Forming Enzyme MenE.,Evans CE, Si Y, Matarlo JS, Yin Y, French JB, Tonge PJ, Tan DS Biochemistry. 2019 Apr 9;58(14):1918-1930. doi: 10.1021/acs.biochem.9b00003. Epub, 2019 Mar 26. PMID:30912442<ref>PMID:30912442</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6nj0" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: O-succinylbenzoate--CoA ligase]]
| + | [[Category: French JB]] |
| - | [[Category: French, J B]] | + | [[Category: Si Y]] |
| - | [[Category: Si, Y]] | + | [[Category: Tonge PJ]] |
| - | [[Category: Tonge, P J]] | + | [[Category: Yin Y]] |
| - | [[Category: Yin, Y]] | + | |
| - | [[Category: E. coli]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Menaquinone]]
| + | |
| - | [[Category: Mene]]
| + | |
