Kessl Jacques J, Meshnick Steven R, Trumpower Bernard L
Center for Retrovirus Research, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
Trends Parasitol. 2007 Oct;23(10):494-501. doi: 10.1016/j.pt.2007.08.004. Epub 2007 Sep 7.
Atovaquone is a substituted hydroxynaphthoquinone that is used therapeutically for treating Plasmodium falciparum malaria, Pneumocystis jirovecii pneumonia and Toxoplasma gondii toxoplasmosis. It is thought to act on these organisms by inhibiting parasite and fungal respiration by binding to the cytochrome bc1 complex. The recent, growing failure of atovaquone treatment and increased mortality of patients with malaria or Pneumocystis pneumonia has been linked to the appearance of mutations in the cytochrome b gene. To better understand the molecular basis of drug resistance, we have developed the yeast and bovine bc1 complexes as surrogates to model the molecular interaction of atovaquone with human and resistant pathogen enzymes.
阿托伐醌是一种取代的羟基萘醌，用于治疗恶性疟原虫疟疾、耶氏肺孢子菌肺炎和弓形虫病。据认为，它通过与细胞色素bc1复合物结合来抑制寄生虫和真菌的呼吸作用，从而对这些生物体产生作用。最近，阿托伐醌治疗的失败率不断上升，疟疾或肺孢子菌肺炎患者的死亡率增加，这与细胞色素b基因突变的出现有关。为了更好地理解耐药性的分子基础，我们开发了酵母和牛bc1复合物作为替代物，以模拟阿托伐醌与人类及耐药病原体酶的分子相互作用。
