How azide inhibits ATP hydrolysis by the F-ATPases.

TitleHow azide inhibits ATP hydrolysis by the F-ATPases.
Publication TypeJournal Article
Year of Publication2006
AuthorsBowler, MW, Montgomery, MG, Leslie, AGW, Walker, JE
JournalProc Natl Acad Sci U S A
Volume103
Issue23
Pagination8646-9
Date Published2006 Jun 06
ISSN0027-8424
KeywordsAdenosine Triphosphate, Animals, Azides, Binding Sites, Cattle, Hydrolysis, Models, Molecular, Proton-Translocating ATPases
Abstract

In the structure of bovine F1-ATPase determined at 1.95-A resolution with crystals grown in the presence of ADP, 5'-adenylyl-imidodiphosphate, and azide, the azide anion interacts with the beta-phosphate of ADP and with residues in the ADP-binding catalytic subunit, betaDP. It occupies a position between the catalytically essential amino acids, beta-Lys-162 in the P loop and the "arginine finger" residue, alpha-Arg-373, similar to the site occupied by the gamma-phosphate in the ATP-binding subunit, betaTP. Its presence in the betaDP-subunit tightens the binding of the side chains to the nucleotide, enhancing its affinity and thereby stabilizing the state with bound ADP. This mechanism of inhibition appears to be common to many other ATPases, including ABC transporters, SecA, and DNA topoisomerase IIalpha. It also explains the stimulatory effect of azide on ATP-sensitive potassium channels by enhancing the binding of ADP.

DOI10.1073/pnas.0602915103
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.0602915103
PubMed ID16728506
PubMed Central IDPMC1469772
Grant ListMC_U105184325 / / Medical Research Council / United Kingdom
MC_U105663150 / / Medical Research Council / United Kingdom