This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6msn
From Proteopedia
(Difference between revisions)
| (3 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of cytosolic fumarate hydratase from Leishmania major in a complex with inhibitor thiomalate== | |
| + | <StructureSection load='6msn' size='340' side='right'caption='[[6msn]], [[Resolution|resolution]] 1.59Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6msn]] is a 2 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=6MSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MSN 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]] 1.591Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JYD:(2S)-2-sulfanylbutanedioic+acid'>JYD</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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=6msn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6msn OCA], [https://pdbe.org/6msn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6msn RCSB], [https://www.ebi.ac.uk/pdbsum/6msn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6msn ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FUM2_LEIMA FUM2_LEIMA] | ||
| + | <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 6msn" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Leishmania major]] | ||
| + | [[Category: Drennan CL]] | ||
| + | [[Category: Feliciano PR]] | ||
| + | [[Category: Nonato MC]] | ||
Current revision
Crystal structure of cytosolic fumarate hydratase from Leishmania major in a complex with inhibitor thiomalate
| |||||||||||
