Edlind T D, Henry K W, Metera K A, Katiyar S K
MCP Hahnemann University, Philadelphia, Pennsylvania 19129, USA.
Med Mycol. 2001 Jun;39(3):299-302. doi: 10.1080/mmy.39.3.299.302.
We have cloned and sequenced the Aspergillus fumigatus CYP51 gene which encodes the target of azole antifungal agents, namely cytochrome P450 sterol 14alpha-demethylase. Since A. fumigatus is intrinsically resistant to the widely used azole fluconazole, we compared its predicted CYP51 sequence to the CYP51 sequences from fluconazole-susceptible and resistant Candida albicans. This analysis generated specific hypotheses regarding the basis for A. fumigatus fluconazole resistance; in particular, A. fumigatus residue Ile301 corresponds to C. albicans residue Thr315 which is mutated to Ala in resistant strains and is proposed to hydrogen bond with the sterol substrate.
我们已经克隆并测序了烟曲霉CYP51基因，该基因编码唑类抗真菌药物的作用靶点，即细胞色素P450甾醇14α-去甲基酶。由于烟曲霉对广泛使用的唑类药物氟康唑具有内在抗性，我们将其预测的CYP51序列与氟康唑敏感和耐药的白色念珠菌的CYP51序列进行了比较。该分析产生了关于烟曲霉对氟康唑耐药性基础的特定假设；特别是，烟曲霉的Ile301残基对应于白色念珠菌的Thr315残基，该残基在耐药菌株中突变为Ala，并被认为与甾醇底物形成氢键。
