5f92: Difference between revisions

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 ==Fumarate hydratase of Mycobacterium tuberculosis in complex with formate==
-<StructureSection load='5f92' size='340' side='right' caption='[[5f92]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
+<StructureSection load='5f92' size='340' side='right'caption='[[5f92]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5f92]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F92 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5f92]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F92 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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]] 1.859&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f91|5f91]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5f92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f92 OCA], [https://pdbe.org/5f92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f92 RCSB], [https://www.ebi.ac.uk/pdbsum/5f92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f92 ProSAT]</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=5f92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f92 OCA], [http://pdbe.org/5f92 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f92 RCSB], [http://www.ebi.ac.uk/pdbsum/5f92 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f92 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/FUMC_MYCTO FUMC_MYCTO]] Catalyzes the reversible addition of water to fumarate to give L-malate.
+[https://www.uniprot.org/uniprot/FUMC_MYCTU FUMC_MYCTU] Catalyzes the reversible addition of water to fumarate to give L-malate.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Enzymes in essential metabolic pathways are attractive targets for the treatment of bacterial diseases, but in many cases, the presence of homologous human enzymes makes them impractical candidates for drug development. Fumarate hydratase, an essential enzyme in the tricarboxylic acid (TCA) cycle, has been identified as one such potential therapeutic target in tuberculosis. We report the discovery of the first small molecule inhibitor, to our knowledge, of the Mycobacterium tuberculosis fumarate hydratase. A crystal structure at 2.0-A resolution of the compound in complex with the protein establishes the existence of a previously unidentified allosteric regulatory site. This allosteric site allows for selective inhibition with respect to the homologous human enzyme. We observe a unique binding mode in which two inhibitor molecules interact within the allosteric site, driving significant conformational changes that preclude simultaneous substrate and inhibitor binding. Our results demonstrate the selective inhibition of a highly conserved metabolic enzyme that contains identical active site residues in both the host and the pathogen.
-Selective small molecule inhibitor of the Mycobacterium tuberculosis fumarate hydratase reveals an allosteric regulatory site.,Kasbekar M, Fischer G, Mott BT, Yasgar A, Hyvonen M, Boshoff HI, Abell C, Barry CE 3rd, Thomas CJ Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7503-8. doi:, 10.1073/pnas.1600630113. Epub 2016 Jun 20. PMID:27325754<ref>PMID:27325754</ref>
+==See Also==
+*[[Fumarase|Fumarase]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 5f92" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Fumarate hydratase]]
+[[Category: Large Structures]]
-[[Category: Abell, C]]
+[[Category: Mycobacterium tuberculosis CDC1551]]
-[[Category: Barry, C E]]
+[[Category: Abell C]]
-[[Category: Boshoff, H I]]
+[[Category: Barry CE]]
-[[Category: Fischer, G]]
+[[Category: Boshoff HI]]
-[[Category: Hyvonen, M]]
+[[Category: Fischer G]]
-[[Category: Kasbekar, M]]
+[[Category: Hyvonen M]]
-[[Category: Mott, B T]]
+[[Category: Kasbekar M]]
-[[Category: Thomas, C J]]
+[[Category: Mott BT]]
-[[Category: Yasgar, A]]
+[[Category: Thomas CJ]]
-[[Category: Hydratase]]
+[[Category: Yasgar A]]
-[[Category: Lyase]]
-[[Category: Metabolism]]
-[[Category: Tuberculosis]]