1EFR

BOVINE MITOCHONDRIAL F1-ATPASE COMPLEXED WITH THE PEPTIDE ANTIBIOTIC EFRAPEPTIN

Summary for 1EFR

• Entry DOI: 10.2210/pdb1efr/pdb
• Related: 1BMF 1COW
• Related PRD ID: PRD_000186
• Descriptor: BOVINE MITOCHONDRIAL F1-ATPASE SUBUNIT ALPHA, BOVINE MITOCHONDRIAL F1-ATPASE SUBUNIT BETA, BOVINE MITOCHONDRIAL F1-ATPASE SUBUNIT GAMMA, ... (8 entities in total)
• Functional Keywords: antibiotic, atp phosphorylase, hydrogen ion transport, atp synthase, f1-atpase, ionophore, hydrolase-antibiotic complex, efrapeptin, f1-atpase-antibiotic complex, hydrolase/antibiotic
• Biological source: TOLYPOCLADIUM INFLATUM; More
• Cellular location: Mitochondrion inner membrane : P19483; Mitochondrion: P00829 P05631
• Total number of polymer chains: 8
• Total formula weight: 355531.33

Authors

Abrahams, J.P.,Buchanan, S.K.,Van Raaij, M.J.,Fearnley, I.M.,Leslie, A.G.W.,Walker, J.E. (deposition date: 1996-05-24, release date: 1997-02-12, Last modification date: 2023-08-09)

Primary citation

Abrahams, J.P.,Buchanan, S.K.,Van Raaij, M.J.,Fearnley, I.M.,Leslie, A.G.,Walker, J.E.
The Structure of Bovine F1-ATPase Complexed with the Peptide Antibiotic Efrapeptin.
Proc.Natl.Acad.Sci.USA, 93:9420-, 1996

PubMed Abstract: In the previously determined structure of mitochondrial F1-ATPase determined with crystals grown in the presence of adenylyl-imidodiphosphate (AMP-PNP) and ADP, the three catalytic beta-subunits have different conformations and nucleotide occupancies. AMP-PNP and ADP are bound to subunits beta TP and beta DP, respectively, and the third beta-subunit (beta E) has no bound nucleotide. The efrapeptins are a closely related family of modified linear peptides containing 15 amino acids that inhibit both ATP synthesis and hydrolysis by binding to the F1 catalytic domain of F1F0-ATP synthase. In crystals of F1-ATPase grown in the presence of both nucleotides and inhibitor, efrapeptin is bound to a unique site in the central cavity of the enzyme. Its binding is associated with small structural changes in side chains of F1-ATPase around the binding pocket. Efrapeptin makes hydrophobic contacts with the alpha-helical structure in the gamma-subunit, which traverses the cavity, and with subunit beta E and the two adjacent alpha-subunits. Two intermolecular hydrogen bonds could also form. Intramolecular hydrogen bonds probably help to stabilize efrapeptin's two domains (residues 1-6 and 9-15, respectively), which are connected by a flexible region (beta Ala-7 and Gly-8). Efrapeptin appears to inhibit F1-ATPase by blocking the conversion of subunit beta E to a nucleotide binding conformation, as would be required by an enzyme mechanism involving cyclic interconversion of catalytic sites.

PubMed: 8790345
DOI: 10.1073/PNAS.93.18.9420

Experimental method

X-RAY DIFFRACTION (3.1 Å)