6mso: Difference between revisions
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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]] 2.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6mso]] is a 4 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MSO FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6mso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mso OCA], [http://pdbe.org/6mso PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mso RCSB], [http://www.ebi.ac.uk/pdbsum/6mso PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mso ProSAT]</span></td></tr> | |||
</table> | |||
<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6mso" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Fumarate hydratase]] | |||
[[Category: Drennan, C L]] | |||
[[Category: Feliciano, P R]] | |||
[[Category: Nonato, M C]] | |||
[[Category: Inhibitor]] | |||
[[Category: Lyase]] | |||
[[Category: Lyase-lyase inhibitor complex]] | |||
[[Category: Mitochondrial]] | |||
Revision as of 08:44, 30 January 2019
Crystal structure of mitochondrial fumarate hydratase from Leishmania major in a complex with inhibitor thiomalate
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