4pd4
From Proteopedia
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==Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action== | ==Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action== | ||
| - | <StructureSection load='4pd4' size='340' side='right' caption='[[4pd4]], [[Resolution|resolution]] 3.04Å' scene=''> | + | <StructureSection load='4pd4' size='340' side='right'caption='[[4pd4]], [[Resolution|resolution]] 3.04Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4pd4]] is a | + | <table><tr><td colspan='2'>[[4pd4]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PD4 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=3PH:1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE'>3PH</scene>, <scene name='pdbligand=AOQ:2-[TRANS-4-(4-CHLOROPHENYL)CYCLOHEXYL]-3-HYDROXYNAPHTHALENE-1,4-DIONE'>AOQ</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=UMQ:UNDECYL-MALTOSIDE'>UMQ</scene>, <scene name='pdbligand=UQ6:5-(3,7,11,15,19,23-HEXAMETHYL-TETRACOSA-2,6,10,14,18,22-HEXAENYL)-2,3-DIMETHOXY-6-METHYL-BENZENE-1,4-DIOL'>UQ6</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.04Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=3PH:1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE'>3PH</scene>, <scene name='pdbligand=AOQ:2-[TRANS-4-(4-CHLOROPHENYL)CYCLOHEXYL]-3-HYDROXYNAPHTHALENE-1,4-DIONE'>AOQ</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=UMQ:UNDECYL-MALTOSIDE'>UMQ</scene>, <scene name='pdbligand=UQ6:5-(3,7,11,15,19,23-HEXAMETHYL-TETRACOSA-2,6,10,14,18,22-HEXAENYL)-2,3-DIMETHOXY-6-METHYL-BENZENE-1,4-DIOL'>UQ6</scene></td></tr> | |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4pd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pd4 OCA], [https://pdbe.org/4pd4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pd4 RCSB], [https://www.ebi.ac.uk/pdbsum/4pd4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pd4 ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KV5AE_MOUSE KV5AE_MOUSE] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Atovaquone, a substituted hydroxynaphthoquinone, is a potent antimalarial drug that acts by inhibiting the parasite's mitochondrial cytochrome bc1 complex (cyt bc1). Mutations in cyt bc1 confer atovaquone resistance. Here we describe the X-ray structure of mitochondrial cyt bc1 from Saccharomyces cerevisiae with atovaquone bound in the catalytic Qo site, at 3.0-A resolution. A polarized H-bond to His181 of the Rieske protein in cyt bc1 traps the ionized hydroxyl group of the drug. Side chains of highly conserved cytochrome b residues establish multiple non-polar interactions with the napththoquinone group, whereas less-conserved residues are in contact with atovaquone's cyclohexyl-chlorophenyl tail. Our structural analysis reveals the molecular basis of atovaquone's broad target spectrum, species-specific efficacies and acquired resistances, and may aid drug development to control the spread of resistant parasites. | ||
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| + | Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action.,Birth D, Kao WC, Hunte C Nat Commun. 2014 Jun 4;5:4029. doi: 10.1038/ncomms5029. PMID:24893593<ref>PMID:24893593</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4pd4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mus musculus]] |
| - | [[Category: | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: | + | [[Category: Birth D]] |
| - | [[Category: | + | [[Category: Hunte C]] |
| - | [[Category: | + | [[Category: Kao W-C]] |
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Current revision
Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action
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