5ec4

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==Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis in complex with inhibitor 13g and CoA==
==Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis in complex with inhibitor 13g and CoA==
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<StructureSection load='5ec4' size='340' side='right' caption='[[5ec4]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
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<StructureSection load='5ec4' size='340' side='right'caption='[[5ec4]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5ec4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EC4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EC4 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5ec4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EC4 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5LQ:5-(3-CHLOROPHENYL)-4-METHYL-~{N}-(3-MORPHOLIN-4-YLPROPYL)-1,1-BIS(OXIDANYLIDENE)-1,2-THIAZOL-3-AMINE'>5LQ</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.21&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ebv|5ebv]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5LQ:5-(3-CHLOROPHENYL)-4-METHYL-~{N}-(3-MORPHOLIN-4-YLPROPYL)-1,1-BIS(OXIDANYLIDENE)-1,2-THIAZOL-3-AMINE'>5LQ</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene></td></tr>
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<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=5ec4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ec4 OCA], [http://pdbe.org/5ec4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ec4 RCSB], [http://www.ebi.ac.uk/pdbsum/5ec4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ec4 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ec4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ec4 OCA], [https://pdbe.org/5ec4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ec4 RCSB], [https://www.ebi.ac.uk/pdbsum/5ec4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ec4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[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>
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A major cause of tuberculosis (TB) resistance to the aminoglycoside kanamycin (KAN) is the Mycobacterium tuberculosis (Mtb) acetyltransferase Eis. Upregulation of this enzyme is responsible for inactivation of KAN through acetylation of its amino groups. A 123000-compound high-throughput screen (HTS) yielded several small-molecule Eis inhibitors that share an isothiazole S,S-dioxide heterocyclic core. These were investigated for their structure-activity relationships. Crystal structures of Eis in complex with two potent inhibitors show that these molecules are bound in the conformationally adaptable aminoglycoside binding site of the enzyme, thereby obstructing binding of KAN for acetylation. Importantly, we demonstrate that several Eis inhibitors, when used in combination with KAN against resistant Mtb, efficiently overcome KAN resistance. This approach paves the way toward development of novel combination therapies against aminoglycoside-resistant TB.
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Potent Inhibitors of Acetyltransferase Eis Overcome Kanamycin Resistance in Mycobacterium tuberculosis.,Willby MJ, Green KD, Gajadeera CS, Hou C, Tsodikov OV, Posey JE, Garneau-Tsodikova S ACS Chem Biol. 2016 Apr 7. PMID:27010218<ref>PMID:27010218</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5ec4" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Gajadeera, C S]]
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[[Category: Large Structures]]
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[[Category: Garneau-Tsodikova, S]]
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[[Category: Mycobacterium tuberculosis H37Rv]]
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[[Category: Hou, C]]
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[[Category: Gajadeera CS]]
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[[Category: Tsodikov, O V]]
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[[Category: Garneau-Tsodikova S]]
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[[Category: Aminoglycoside]]
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[[Category: Hou C]]
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[[Category: Resistance]]
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[[Category: Tsodikov OV]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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[[Category: Tuberculosis]]
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Current revision

Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis in complex with inhibitor 13g and CoA

PDB ID 5ec4

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