8f51: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8f51]] 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=8F51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F51 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8f51]] 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=8F51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F51 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=YMZ:MEFLOQUINE'>YMZ</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=YMZ:MEFLOQUINE'>YMZ</scene></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=8f51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f51 OCA], [https://pdbe.org/8f51 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f51 RCSB], [https://www.ebi.ac.uk/pdbsum/8f51 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f51 ProSAT]</span></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=8f51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f51 OCA], [https://pdbe.org/8f51 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f51 RCSB], [https://www.ebi.ac.uk/pdbsum/8f51 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f51 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 13:30, 25 October 2023
Crystal structure of acetyltransferase Eis from M. tuberculosis in complex with mefloquineCrystal structure of acetyltransferase Eis from M. tuberculosis in complex with mefloquine
Structural highlights
FunctionEIS_MYCTU May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.[1] Publication Abstract from PubMedOver one and a half million people die of tuberculosis (TB) each year. Multidrug-resistant TB infections are especially dangerous, and new drugs are needed to combat them. The high cost and complexity of drug development make repositioning of drugs that are already in clinical use for other indications a potentially time- and money-saving avenue. In this study, we identified among existing drugs five compounds: azelastine, venlafaxine, chloroquine, mefloquine, and proguanil as inhibitors of acetyltransferase Eis from Mycobacterium tuberculosis, a causative agent of TB. Eis upregulation is a cause of clinically relevant resistance of TB to kanamycin, which is inactivated by Eis-catalyzed acetylation. Crystal structures of these drugs as well as chlorhexidine in complexes with Eis showed that these inhibitors were bound in the aminoglycoside binding cavity, consistent with their established modes of inhibition with respect to kanamycin. Among three additionally synthesized compounds, a proguanil analogue, designed based on the crystal structure of the Eis-proguanil complex, was 3-fold more potent than proguanil. The crystal structures of these compounds in complexes with Eis explained their inhibitory potencies. These initial efforts in rational drug repositioning can serve as a starting point in further development of Eis inhibitors. Discovery and Mechanistic Analysis of Structurally Diverse Inhibitors of Acetyltransferase Eis among FDA-Approved Drugs.,Pang AH, Green KD, Punetha A, Thamban Chandrika N, Howard KC, Garneau-Tsodikova S, Tsodikov OV Biochemistry. 2023 Jan 19. doi: 10.1021/acs.biochem.2c00658. PMID:36657084[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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