Cytochrome b (protozoal mitochondrial cytochrome b) (Cyt b)

Cytochrome b is the central redox catalytic subunit of the mitochondrial cytochrome bc1 complex (complex III) in protozoa, crucial for electron transfer between ubiquinol and cytochrome c, thereby coupling electron transport with proton translocation to generate a proton gradient used for ATP synthesis[2][3][5]. Protozoal cytochrome b is a validated therapeutic target for antiparasitic drugs such as atovaquone in malaria and related compounds in Chagas disease and leishmaniasis[2][4][6][7]. The structure of cytochrome b includes several transmembrane helices and two heme groups (bH and bL), with Q_o (ubiquinol oxidation) and Q_i (ubiquinone reduction) binding sites that serve as binding targets for a range of ETC inhibitors[1][2][3]. Mutations in the cytochrome b gene confer resistance to these drugs and present major challenges for therapy[4][6][7]. Cytochrome b inhibitors are important for their antiparasitic activity but require careful design to avoid off-target effects on the host and slow resistance[4][6][7].

Other names

Mitochondrial cytochrome bApocytochrome bCytbCytochrome b of electron transport complex IIIProtozoal cytochrome b

Inhibition of electron transfer from ubiquinol to cytochrome c, disrupting mitochondrial ATP production and collapsing mitochondrial membrane potential (mechanism for atovaquone, antimycin A, ELQ compounds, and others) Competitive binding to Q_o or Q_i sites, interfering with proton motive force generation and parasite survival