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==Crystal structure of mitochondrial fumarate hydratase from Leishmania major in a complex with inhibitor thiomalate==
<StructureSection load='6mso' size='340' side='right'caption='[[6mso]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mso]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MSO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MSO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.053&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JYD:(2S)-2-sulfanylbutanedioic+acid'>JYD</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=6mso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mso OCA], [https://pdbe.org/6mso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mso RCSB], [https://www.ebi.ac.uk/pdbsum/6mso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mso ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FUM1_LEIMA FUM1_LEIMA] Catalyzes the reversible hydration of fumarate to (S)-malate (PubMed:22569531, PubMed:30645090). Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH (Probable).<ref>PMID:22569531</ref> <ref>PMID:30645090</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Leishmaniases affect the poorest people on earth and have no effective drug therapy. Here, we present the crystal structure of the mitochondrial isoform of class I fumarate hydratase (FH) from Leishmania major and compare it to the previously determined cytosolic Leishmania major isoform. We further describe the mechanism of action of the first class-specific FH inhibitor, 2-thiomalate, through X-ray crystallography and inhibition assays. Our crystal structures of both FH isoforms with inhibitor bound at 2.05 A resolution and 1.60 A resolution show high structural similarity. These structures further reveal that the selectivity of 2-thiomalate for class I FHs is due to direct coordination of the inhibitor to the unique Fe of the catalytic [4Fe-4S] cluster that is found in class I parasitic FHs but is absent from class II human FH. These studies provide the structural scaffold in order to exploit class I FHs as potential drug targets against leishmaniases as well as Chagas diseases, sleeping sickness and malaria.

Crystal structures of fumarate hydratases from Leishmania major in a complex with inhibitor 2-thiomalate.,Feliciano PR, Drennan CL, Nonato MC ACS Chem Biol. 2019 Jan 15. doi: 10.1021/acschembio.8b00972. PMID:30645090<ref>PMID:30645090</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mso" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania major]]
[[Category: Drennan CL]]
[[Category: Feliciano PR]]
[[Category: Nonato MC]]