Effect of famoxadone on photoinduced electron transfer between the iron-sulfur center and cytochrome c1 in the cytochrome bc1 complex.
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.
Xiao
Kunhong
K
Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma 74078, USA.
Engstrom
Gregory
G
Rajagukguk
Sany
S
Yu
Chang-An
CA
Yu
Linda
L
Durham
Bill
B
Millett
Francis
F
D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D003575:Cytochromes c1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D007700:Kinetics; D008689:Methacrylates; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010080:Oxazoles / Q000494:pharmacology*; D010777:Photochemistry; D011487:Protein Conformation; D011743:Pyrimidines / Q000494:pharmacology; D000073739:Strobilurins
D000179:Acrylates; D004791:Enzyme Inhibitors; D007506:Iron-Sulfur Proteins; D008689:Methacrylates; D010080:Oxazoles; D011743:Pyrimidines; D000073739:Strobilurins; D003575:Cytochromes c1; D014450:Electron Transport Complex III; C087670:azoxystrobin; C401929:famoxadone