4pd4 | pdb_00004pd4

Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action

spinqualitylabelsall models 4pd4, resolution 3.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pd4 is a 10 chain structure with sequence from Mus musculus and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.04Å Ligands: 3PE, 3PH, AOQ, FES, HEM, UMQ, UQ6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KV5AE_MOUSE 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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