5iv0
From Proteopedia
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== Function == | == Function == | ||
[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> | [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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| - | == Publication Abstract from PubMed == | ||
| - | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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| - | <div class="pdbe-citations 5iv0" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal structure of Eis from Mycobacterium tuberculosis in complex with sulfonamide inhibitor 39 and coenzyme A
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