Evolutionary trace analysis of CYP51 family: implication for site-directed mutagenesis and novel antifungal drug design
Lanosterol 14α-demethylase (CYP51) is an essential enzyme in the fungal life cycle and also an important target for the antifungal drug development. Based on the multiple sequence alignments of CYP51 family, an evolutionary tree of the CYP51 family was constructed by the evolutionary trace (ET) method. The identified trace residues could provide a reliable and rational guide to the design of CYP51 mutations and give more information about the detailed mechanism of substrate (drug) recognition and binding. The reliability of ET analysis to identify residues of functional importance was validated by the reported site-directed mutagenesis studies of CYP51s. Several residues in the active site were also validated by our mutagenesis studies. Mapping the identified trace residues onto the active site of the modeled structure of Candida albicans CYP51 (CACYP51) may provide useful information for the design of novel antifungal agents.
Chunquan Sheng Wei Guo Wannian Zhang Shuanghong Chen Haitao Ji Guoqiang Dong Xiaoyin Che Wenya Wang Zhenyuan Miao Jianzhong Yao Jiaguo Lü
School of Pharmacy, Military Key Laboratory of Medicinal Chemistry, Second Military Medical Universi Naval Medical Research Institute, 880 Xiangying Road, Shanghai 200433, Peoples Republic of China Department of Chemistry, Department of Biochemistry, Molecular Biology, and Cell Biology, and Center
国际会议
武汉
英文
6-11
2010-09-01（万方平台首次上网日期，不代表论文的发表时间）