5tvj
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis in complex with CoA and inhibitor 2k*: 1-(4-fluorophenyl)-2-[2-(4-methylphenyl)-2-oxoethyl]pyrrolo[1,2-a]pyrazin-2-ium== | |
| + | <StructureSection load='5tvj' size='340' side='right' caption='[[5tvj]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5tvj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TVJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7LF:1-(4-FLUOROPHENYL)-2-[2-(4-METHYLPHENYL)-2-OXOETHYL]PYRROLO[1,2-A]PYRAZIN-2-IUM'>7LF</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5tvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tvj OCA], [http://pdbe.org/5tvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tvj RCSB], [http://www.ebi.ac.uk/pdbsum/5tvj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tvj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/EIS_MYCTU EIS_MYCTU]] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.<ref>PMID:10629183</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tuberculosis (TB) remains one of the leading causes of mortality worldwide. Hence, the identification of highly effective antitubercular drugs with novel modes of action is crucial. In this paper, we report the discovery and development of pyrrolo[1,5-a]pyrazine-based analogues as highly potent inhibitors of the Mycobacterium tuberculosis (Mtb) acetyltransferase enhanced intracellular survival (Eis), whose up-regulation causes clinically observed resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN). We performed a structure-activity relationship (SAR) study to optimize these compounds as potent Eis inhibitors both against purified enzyme and in mycobacterial cells. A crystal structure of Eis in complex with one of the most potent inhibitors reveals that the compound is bound to Eis in the AG binding pocket, serving as the structural basis for the SAR. These Eis inhibitors have no observed cytotoxicity to mammalian cells and are promising leads for the development of innovative AG adjuvant therapies against drug-resistant TB. | ||
| - | + | Combating Enhanced Intracellular Survival (Eis)-Mediated Kanamycin Resistance of Mycobacterium tuberculosis by Novel Pyrrolo[1,5-a]pyrazine-Based Eis Inhibitors.,Garzan A, Willby MJ, Ngo HX, Gajadeera CS, Green KD, Holbrook SY, Hou C, Posey JE, Tsodikov OV, Garneau-Tsodikova S ACS Infect Dis. 2017 Feb 17. doi: 10.1021/acsinfecdis.6b00193. PMID:28192916<ref>PMID:28192916</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5tvj" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Gajadeera, C S]] | ||
| + | [[Category: Garneau-Tsodikova, S]] | ||
| + | [[Category: Garzan, A]] | ||
| + | [[Category: Hou, C]] | ||
| + | [[Category: Tsodikov, O V]] | ||
| + | [[Category: Acetyltransferase]] | ||
| + | [[Category: Aminoglycoside]] | ||
| + | [[Category: Resistance]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 09:41, 11 March 2017
Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis in complex with CoA and inhibitor 2k*: 1-(4-fluorophenyl)-2-[2-(4-methylphenyl)-2-oxoethyl]pyrrolo[1,2-a]pyrazin-2-ium
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