4kw5
From Proteopedia
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| - | + | ==M. tuberculosis DprE1 in complex with inhibitor TCA1== | |
| - | + | <StructureSection load='4kw5' size='340' side='right' caption='[[4kw5]], [[Resolution|resolution]] 2.61Å' scene=''> | |
| - | { | + | == Structural highlights == |
| + | <table><tr><td colspan='2'>[[4kw5]] is a 2 chain structure with sequence from [http://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=4KW5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KW5 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1W6:ETHYL+({2-[(1,3-BENZOTHIAZOL-2-YLCARBONYL)AMINO]THIOPHEN-3-YL}CARBONYL)CARBAMATE'>1W6</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fdo|4fdo]], [[4fdn|4fdn]], [[4feh|4feh]], [[4fdp|4fdp]], [[4ff6|4ff6]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rv3790, RVBD_3790 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 Mycobacterium tuberculosis H37Rv])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Decaprenylphospho-beta-D-ribofuranose_2-oxidase Decaprenylphospho-beta-D-ribofuranose 2-oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.98.3 1.1.98.3] </span></td></tr> | ||
| + | <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=4kw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kw5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kw5 RCSB], [http://www.ebi.ac.uk/pdbsum/4kw5 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A cell-based phenotypic screen for inhibitors of biofilm formation in mycobacteria identified the small molecule TCA1, which has bactericidal activity against both drug-susceptible and -resistant Mycobacterium tuberculosis (Mtb) and sterilizes Mtb in vitro combined with rifampicin or isoniazid. In addition, TCA1 has bactericidal activity against nonreplicating Mtb in vitro and is efficacious in acute and chronic Mtb infection mouse models both alone and combined with rifampicin or isoniazid. Transcriptional analysis revealed that TCA1 down-regulates genes known to be involved in Mtb persistence. Genetic and affinity-based methods identified decaprenyl-phosphoryl-beta-D-ribofuranose oxidoreductase DprE1 and MoeW, enzymes involved in cell wall and molybdenum cofactor biosynthesis, respectively, as targets responsible for the activity of TCA1. These in vitro and in vivo results indicate that this compound functions by a unique mechanism and suggest that TCA1 may lead to the development of a class of antituberculosis agents. | ||
| - | + | Identification of a small molecule with activity against drug-resistant and persistent tuberculosis.,Wang F, Sambandan D, Halder R, Wang J, Batt SM, Weinrick B, Ahmad I, Yang P, Zhang Y, Kim J, Hassani M, Huszar S, Trefzer C, Ma Z, Kaneko T, Mdluli KE, Franzblau S, Chatterjee AK, Johnson K, Mikusova K, Besra GS, Futterer K, Jacobs WR Jr, Schultz PG Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):E2510-7. doi:, 10.1073/pnas.1309171110. Epub 2013 Jun 17. PMID:23776209<ref>PMID:23776209</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Decaprenylphospho-beta-D-ribofuranose 2-oxidase]] | [[Category: Decaprenylphospho-beta-D-ribofuranose 2-oxidase]] | ||
[[Category: Mycobacterium tuberculosis h37rv]] | [[Category: Mycobacterium tuberculosis h37rv]] | ||
| - | [[Category: Batt, S M | + | [[Category: Batt, S M]] |
| - | [[Category: Besra, G S | + | [[Category: Besra, G S]] |
| - | [[Category: Futterer, K | + | [[Category: Futterer, K]] |
[[Category: Alpha/beta fold]] | [[Category: Alpha/beta fold]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
Revision as of 15:34, 21 December 2014
M. tuberculosis DprE1 in complex with inhibitor TCA1
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