How azide inhibits ATP hydrolysis by the F-ATPases

In the structure of bovine F-1-ATPase determined at 1.95-angstrom resolution with crystals grown in the presence of ADP, 5'-adenylylimidodiphosphate, and azide, the azide anion interacts with the beta-phosphate of ADP and with residues in the ADP-binding catalytic subunit, beta(DP). 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, beta(TP). Its presence in the beta(DP)-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 II alpha. It also explains the stimulatory effect of azide on ATP-sensitive potassium channels by enhancing the binding of ADP.