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6s43
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Fumarate hydratase of Mycobacterium tuberculosis in complex with formate and allosteric modulator N-(5-(Azocan-1-ylsulfonyl)-2-methoxyphenyl)-2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetamide== | |
| + | <StructureSection load='6s43' size='340' side='right'caption='[[6s43]], [[Resolution|resolution]] 1.42Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6s43]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S43 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S43 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=KUE:~{N}-[5-(azocan-1-ylsulfonyl)-2-methoxy-phenyl]-2-(4-oxidanylidene-3~{H}-phthalazin-1-yl)ethanamide'>KUE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fum, fumC, DSI35_09545, ERS007663_02818, ERS007679_02635, ERS007688_02307, ERS007722_03256, ERS023446_00966, ERS024276_01230, ERS027646_00759, ERS027653_00188, ERS027654_00515, ERS027659_00384, ERS027661_00671, ERS027666_02275, ERS124361_03161, SAMEA2682864_03539, SAMEA2683035_02636 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fumarate_hydratase Fumarate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.2 4.2.1.2] </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=6s43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s43 OCA], [http://pdbe.org/6s43 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s43 RCSB], [http://www.ebi.ac.uk/pdbsum/6s43 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s43 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/A0A045IXZ8_MYCTX A0A045IXZ8_MYCTX]] Involved in the TCA cycle. Catalyzes the stereospecific interconversion of fumarate to L-malate.[HAMAP-Rule:MF_00743] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | With the growing worldwide prevalence of antibiotic-resistant strains of tuberculosis (TB), new targets are urgently required for the development of treatments with novel modes of action. Fumarate hydratase (fumarase), a vulnerable component of the citric acid cycle in Mycobacterium tuberculosis (Mtb), is a metabolic target that could satisfy this unmet demand. A key challenge in the targeting of Mtb fumarase is its similarity to the human homolog, which shares an identical active site. A potential solution to this selectivity problem was previously found in a high-throughput screening hit that binds in a nonconserved allosteric site. In this work, a structure-activity relationship study was carried out with the determination of further structural biology on the lead series, affording derivatives with sub-micromolar inhibition. Further, the screening of this series against Mtb in vitro identified compounds with potent minimum inhibitory concentrations. | ||
| - | + | Targeting of Fumarate Hydratase from Mycobacterium tuberculosis Using Allosteric Inhibitors with a Dimeric-Binding Mode.,Whitehouse AJ, Libardo MDJ, Kasbekar M, Brear PD, Fischer G, Thomas CJ, Barry CE 3rd, Boshoff HIM, Coyne AG, Abell C J Med Chem. 2019 Dec 12;62(23):10586-10604. doi: 10.1021/acs.jmedchem.9b01203., Epub 2019 Sep 27. PMID:31517489<ref>PMID:31517489</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 6s43" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Fumarate hydratase]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Abell, C]] | [[Category: Abell, C]] | ||
| + | [[Category: Barry, C E]] | ||
| + | [[Category: Boshoff, H I]] | ||
[[Category: Brear, P]] | [[Category: Brear, P]] | ||
| - | [[Category: | + | [[Category: Coyne, A G]] |
| - | [[Category: | + | [[Category: Fischer, G]] |
| - | [[Category: Libardo, M | + | [[Category: Kasbekar, M]] |
| - | [[Category: | + | [[Category: Libardo, M D]] |
| - | [[Category: | + | [[Category: Thomas, C J]] |
| + | [[Category: Whitehouse, A J]] | ||
| + | [[Category: Fumarase]] | ||
| + | [[Category: Lyase]] | ||
Revision as of 13:16, 25 December 2019
Fumarate hydratase of Mycobacterium tuberculosis in complex with formate and allosteric modulator N-(5-(Azocan-1-ylsulfonyl)-2-methoxyphenyl)-2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
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Categories: Fumarate hydratase | Large Structures | Abell, C | Barry, C E | Boshoff, H I | Brear, P | Coyne, A G | Fischer, G | Kasbekar, M | Libardo, M D | Thomas, C J | Whitehouse, A J | Fumarase | Lyase
