View source for 6vuw


==Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT368==
<StructureSection load='6vuw' size='340' side='right'caption='[[6vuw]], [[Resolution|resolution]] 2.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vuw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VUW FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=RNM:(7R)-7-methyl-2-({[(3R)-1-methylpiperidin-3-yl]methyl}sulfanyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-amine'>RNM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">eis, Rv2416c, MTCY253.04 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=6vuw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vuw OCA], [https://pdbe.org/6vuw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vuw RCSB], [https://www.ebi.ac.uk/pdbsum/6vuw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vuw ProSAT]</span></td></tr>
</table>
== 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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The enhanced intracellular survival (Eis) protein of Mycobacterium tuberculosis (Mtb) is a versatile acetyltransferase that multiacetylates aminoglycoside antibiotics abolishing their binding to the bacterial ribosome. When overexpressed as a result of promoter mutations, Eis causes drug resistance. In an attempt to overcome the Eis-mediated kanamycin resistance of Mtb, we designed and optimized structurally unique thieno[2,3-d]pyrimidine Eis inhibitors toward effective kanamycin adjuvant combination therapy. We obtained 12 crystal structures of enzyme-inhibitor complexes, which guided our rational structure-based design of 72 thieno[2,3-d]pyrimidine analogues divided into three families. We evaluated the potency of these inhibitors in vitro as well as their ability to restore the activity of kanamycin in a resistant strain of Mtb, in which Eis was upregulated. Furthermore, we evaluated the metabolic stability of 11 compounds in vitro. This study showcases how structural information can guide Eis inhibitor design.

Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis from Mycobacterium tuberculosis.,Punetha A, Ngo HX, Holbrook SYL, Green KD, Willby MJ, Bonnett SA, Krieger K, Dennis EK, Posey JE, Parish T, Tsodikov OV, Garneau-Tsodikova S ACS Chem Biol. 2020 Jun 19;15(6):1581-1594. doi: 10.1021/acschembio.0c00184. Epub, 2020 May 18. PMID:32421305<ref>PMID:32421305</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vuw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Myctu]]
[[Category: Garneau-Tsodikova, S]]
[[Category: Hou, C]]
[[Category: Ngo, H X]]
[[Category: Punetha, A]]
[[Category: Tsodikov, O V]]
[[Category: Acetyltransferase]]
[[Category: Aminoglycoside]]
[[Category: Competitive]]
[[Category: Kanamycin]]
[[Category: Resistance]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]