4F4S

Structure of the yeast F1Fo ATPase c10 ring with bound oligomycin

Summary for 4F4S

• Entry DOI: 10.2210/pdb4f4s/pdb
• Related: 3U2F 3U2Y 3U32 3UD0
• Descriptor: ATP synthase subunit 9, mitochondrial, Oligomycin A (3 entities in total)
• Functional Keywords: c10 ring, f1fo atp synthase, oligomycin, mitochondria, membrane protein-antibiotic complex, membrane protein/antibiotic
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Mitochondrion membrane; Multi-pass membrane protein (Potential): P61829
• Total number of polymer chains: 10
• Total formula weight: 83441.28

Authors

Symersky, J.,Mueller, D.M. (deposition date: 2012-05-11, release date: 2012-08-15, Last modification date: 2024-10-30)

Primary citation

Symersky, J.,Osowski, D.,Walters, D.E.,Mueller, D.M.
Oligomycin frames a common drug-binding site in the ATP synthase.
Proc.Natl.Acad.Sci.USA, 109:13961-13965, 2012

PubMed Abstract: We report the high-resolution (1.9 Å) crystal structure of oligomycin bound to the subunit c(10) ring of the yeast mitochondrial ATP synthase. Oligomycin binds to the surface of the c(10) ring making contact with two neighboring molecules at a position that explains the inhibitory effect on ATP synthesis. The carboxyl side chain of Glu59, which is essential for proton translocation, forms an H-bond with oligomycin via a bridging water molecule but is otherwise shielded from the aqueous environment. The remaining contacts between oligomycin and subunit c are primarily hydrophobic. The amino acid residues that form the oligomycin-binding site are 100% conserved between human and yeast but are widely different from those in bacterial homologs, thus explaining the differential sensitivity to oligomycin. Prior genetics studies suggest that the oligomycin-binding site overlaps with the binding site of other antibiotics, including those effective against Mycobacterium tuberculosis, and thereby frames a common "drug-binding site." We anticipate that this drug-binding site will serve as an effective target for new antibiotics developed by rational design.

PubMed: 22869738
DOI: 10.1073/pnas.1207912109

Experimental method

X-RAY DIFFRACTION (1.9 Å)