Rieske iron-sulfur protein of the cytochrome bc(1) complex: a potential target for fungicide discovery.
The cytochrome bc(1) complex (complex III, cyt bc(1)) is an essential component of cellular respiration. Cyt bc(1) has three core subunits that are required for its catalytic activity: cytochrome b, cytochrome c(1), and the Rieske iron-sulfur protein (ISP). Although most fungicides inhibit this enzyme by binding to the cytochrome b subunit, resistance to these fungicides has developed rapidly due to their widespread application. Resistance is mainly associated with mutations in cytochrome b, the only subunit encoded by mitochondrial DNA. Recently, the flexibility and motion of the ISP and its essential role in electron transfer have received intense attention; this leads us to propose a new classification of cyt bc(1) inhibitors (three types of Q(o) inhibitors) that mobilize, restrict, or fix the rotation of the ISP. Importantly, the strengths of the ISP-inhibitor interactions correlate with inhibitor activity and the development of resistance to Q(o) inhibitors, thereby offering clues for designing novel cyt bc(1) inhibitors with high potency and a low risk of resistance.
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Luoyu Road 152, 430079 Wuhan, PR China.
Wen-Chao
WC
Yang
Hui
H
Li
Fu
F
Wang
Xiao-Lei
XL
Zhu
Guang-Fu
GF
Yang
D055808:Drug Discovery; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005659:Fungicides, Industrial / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005659:Fungicides, Industrial; C037989:Rieske iron-sulfur protein; D014450:Electron Transport Complex III