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| | ==M. tuberculosis DprE1 in complex with inhibitor TCA1== | | ==M. tuberculosis DprE1 in complex with inhibitor TCA1== |
| - | <StructureSection load='4kw5' size='340' side='right' caption='[[4kw5]], [[Resolution|resolution]] 2.61Å' scene=''> | + | <StructureSection load='4kw5' size='340' side='right'caption='[[4kw5]], [[Resolution|resolution]] 2.61Å' scene=''> |
| | == Structural highlights == | | == 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> | + | <table><tr><td colspan='2'>[[4kw5]] is a 2 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=4KW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.612Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4kw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kw5 OCA], [https://pdbe.org/4kw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kw5 RCSB], [https://www.ebi.ac.uk/pdbsum/4kw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kw5 ProSAT]</span></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>
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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=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> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4kw5" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Decaprenylphospho-beta-D-ribofuranose 2-oxidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Mycobacterium tuberculosis h37rv]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Batt, S M]] | + | [[Category: Batt SM]] |
| - | [[Category: Besra, G S]] | + | [[Category: Besra GS]] |
| - | [[Category: Futterer, K]] | + | [[Category: Futterer K]] |
| - | [[Category: Alpha/beta fold]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
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| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. Identification of a small molecule with activity against drug-resistant and persistent tuberculosis. 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 doi:10.1073/pnas.1309171110
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