Effect of famoxadone on photoinduced electron transfer between the iron-sulfur center and cytochrome c(1) in the cytochrome bc(1) complex

by Xiao, K. H.; Engstrom, G.; Rajagukguk, S.; Yu, C. A.; Yu, L.; Durham, B.; Millett, F.

Famoxadone is a new cytochrome bc(1) Q(o) site inhibitor that immobilizes the iron-sulfur protein (ISP) in the b conformation. The effects of famoxadone on electron transfer between the iron-sulfur center (2Fe-2S) and cyt c(1) were studied using a ruthenium dimer to photoinitiate the reaction. The rate constant for electron transfer in the forward direction from 2Fe-2S to cyt c(1) was found to be 16,000 s(-1) in bovine cyt bc(1). Binding famoxadone decreased this rate constant to 1,480 s(-1), consistent with a decrease in mobility of the ISP. Reverse electron transfer from cyt c(1) to 2Fe-2S was found to be biphasic in bovine cyt bc(1) with rate constants of 90,000 and 7,300 s(-1). In the presence of famoxadone, reverse electron transfer was monophasic with a rate constant of 1,420 s(-1). It appears that the rate constants for the release of the oxidized and reduced ISP from the b conformation are the same in the presence of famoxadone. The effects of famoxadone binding on electron transfer were also studied in a series of Rhodobacter sphaeroides cyt bc(1) mutants involving residues at the interface between the Rieske protein and cyt c(1) and/or cyt b.

Journal
Journal of Biological Chemistry
Volume
278
Issue
13
Year
2003
Start Page
11419-11426
URL
https://dx.doi.org/10.1074/jbc.m211620200
ISBN/ISSN
1083-351X; 0021-9258
DOI
10.1074/jbc.m211620200