MODELING CYTOCHROME-P450 14-ALPHA DEMETHYLASE (CANDIDA-ALBICANS) FROM P450CAM
MODELING CYTOCHROME-P450 14-ALPHA DEMETHYLASE (CANDIDA-ALBICANS) FROM P450CAM
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DOI：
10.1016/0263-7855(94)80086-3
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发表时间：
1994-09-01
影响因子：
2.9
通讯作者：
GRANT, GH
中科院分区：
文献类型：
--
作者：
BOSCOTT, PE;GRANT, GH
细胞色素 P450 14 α 脱甲基酶-白色念珠菌 (P450 CA) 的三级结构是根据两个密切相关的蛋白质的序列比对和恶臭假单胞菌 P450cam 的晶体结构建模的。使用的二级结构预测系统结合了多种算法的信息并训练数据，以提供已知 P450cam 的优化预测。然后使用经过训练的算法来预测其他 P450 序列的二级结构。 P450 CA 与同源序列 P450 14 α 脱甲基酶-酿酒酵母 (66 SD) 和 P450 14 α 脱甲基酶-热带假丝酵母 (72 SD) 之间的比对有助于表面线圈区域的预测。将预测和比对信息相结合，建立 P450 CA 和 P450cam 之间的比对，并将完整的二级结构分配给目标蛋白。该二级结构是从 P450cam 的模板折叠而来的，并且通过分子动力学松弛了预测的结构。模型检查强调了对齐方面的细微调整，正确定位疏水性和亲水性侧链。该模型为几个已知的实验结果提供了解释，并建议进一步的研究可能有助于理解 P450 家族的结构和机制（Porter, T.D. 和 Coon, M.J. Minireview 细胞色素 P450. J. Biol. Chem. 1991, 266, 13469-13472。Waterman, M.R. 细胞色素 P450 细胞分布和结构考虑因素。目前的观点结构生物学 1992，2，384-387。Aoyama，Y.，Yoshida，Y.，Sonondo，Y. 和 Sate，Y。Biochim 的底物侧链与羊毛甾醇 14 α 去甲基酶 (P450 14DM) 活性位点之间的相互作用的结构分析。 1122、251-255。）。
The tertiary structure of cytochrome P450 14 alpha demethylase-Candida albicans (P450 CA) is modeled on the basis of sequence alignment with two closely related proteins and the crystallographic structure of Pseudomonas putida P450cam. The secondary structure prediction system used combines the information from several algorithms and trains the data to offer an optimized prediction of the known P450cam. The trained algorithm was then used to predict the secondary structure of the other P450 sequences. The prediction of the surface coil regions was aided by an alignment between P450 CA and the homologous sequences P450 14 alpha demethylase-Saccharomyes cerevisiae (66 SD) and P450 14 alpha demethylase-Candida tropicalis (72 SD). The prediction and alignment information was combined to establish an alignment between P450 CA and P450cam, and to assign full secondary structure to the target protein. This secondary structure was folded from the template of P450cam and the predicted structure was relaxed by molecular dynamics. Model checking highlighted minor adjustments in the alignment, correctly orienting hydrophobic and hydrophilic side chains. The model offers explanations for several known experimental results and suggests further investigations that may prove fruitful in understanding the structure and mechanisms of the P450 family (Porter, T.D. and Coon, M.J. Minireview cytochrome P450. J. Biol. Chem. 1991, 266, 13469-13472. Waterman, M.R. Cytochrome P450 cellular distribution and structural considerations. Current Opinion in Structural Biology 1992, 2, 384-387. Aoyama, Y., Yoshida, Y., Sonondo, Y. and Sate, Y. Structural analysis of the interaction between the side-chain of substrates and the active site of lanosterol 14 alpha demethyl ase (P450 14DM) of yeast. Biochim. Biophys. Acta 1992, 1122, 251-255.).