5iv0

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<StructureSection load='5iv0' size='340' side='right'caption='[[5iv0]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='5iv0' size='340' side='right'caption='[[5iv0]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5iv0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IV0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IV0 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5iv0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IV0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IV0 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=6E9:N-(3-METHOXYPHENYL)-N-METHYL-2,3-DIOXO-1,2,3,4-TETRAHYDROQUINOXALINE-6-SULFONAMIDE'>6E9</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.1&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">eis, MT2489 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</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=6E9:N-(3-METHOXYPHENYL)-N-METHYL-2,3-DIOXO-1,2,3,4-TETRAHYDROQUINOXALINE-6-SULFONAMIDE'>6E9</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5iv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iv0 OCA], [http://pdbe.org/5iv0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iv0 RCSB], [http://www.ebi.ac.uk/pdbsum/5iv0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iv0 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=5iv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iv0 OCA], [https://pdbe.org/5iv0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iv0 RCSB], [https://www.ebi.ac.uk/pdbsum/5iv0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iv0 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/EIS_MYCTO EIS_MYCTO]] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.
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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 two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. By high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of Mycobacterium tuberculosis acetyltransferase Eis, whose upregulation causes resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN) in Mycobacterium tuberculosis. Rational systematic derivatization of this scaffold to maximize Eis inhibition and abolish the Eis-mediated KAN resistance of M. tuberculosis yielded several highly potent agents. A crystal structure of Eis in complex with one of the most potent inhibitors revealed that the inhibitor bound Eis in the AG-binding pocket held by a conformationally malleable region of Eis (residues 28-37) bearing key hydrophobic residues. These Eis inhibitors are promising leads for preclinical development of innovative AG combination therapies against resistant TB.
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Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis.,Garzan A, Willby MJ, Green KD, Gajadeera CS, Hou C, Tsodikov OV, Posey JE, Garneau-Tsodikova S J Med Chem. 2016 Dec 8;59(23):10619-10628. Epub 2016 Nov 22. PMID:27933949<ref>PMID:27933949</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 5iv0" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Mycto]]
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[[Category: Mycobacterium tuberculosis CDC1551]]
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[[Category: Gajadeera, C S]]
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[[Category: Gajadeera CS]]
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[[Category: Garneau-Tsodikova, S]]
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[[Category: Garneau-Tsodikova S]]
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[[Category: Hou, C]]
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[[Category: Hou C]]
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[[Category: Tsodikov, O V]]
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[[Category: Tsodikov OV]]
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[[Category: Acetyltransferase]]
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[[Category: Inhibitor]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal structure of Eis from Mycobacterium tuberculosis in complex with sulfonamide inhibitor 39 and coenzyme A

PDB ID 5iv0

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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