Class-dependent sequence alignment strategy improves the structural and functional modeling of P450s
Class-dependent sequence alignment strategy improves the structural and functional modeling of P450s
复制标题
DOI：
10.1093/protein/gzl012
复制
发表时间：
2006-08-01
影响因子：
2.4
通讯作者：
Schuler, Mary A.
中科院分区：
文献类型：
--
作者：
Baudry, Jerome;Rupasinghe, Sanjeewa;Schuler, Mary A.
利用与P450晶体结构具有不同程度序列同一性的不同序列比对，研究了获得P450同源模型的不同方法。在本分析中，我们研究了同源模型如何很好地再现已知的晶体结构，以及这些同源模型如何有效地用于再现已知的配体结合模式。与结合I类和II类p450的序列比对相比，区分I类和II类p450的序列比对得到的同源性模型更接近实验晶体结构，更接近已知配体的结合模式。通过构建混合结构模型，模型的质量略有提高，该模型独立于蛋白质的其余部分对p450中三个最可变的区域进行了建模：包括SRS1的B区域，包括SRS2和SRS3的FG区域以及包括SRS6的β 4区域。
Different procedures for obtaining homology models for P450s are investigated using various sequence alignments sharing various levels of sequence identity with available P450 crystal structures. In this analysis, we have investigated how well homology modeling can reproduce known crystal structures as well as how effectively these homology models can be used to reproduce known ligand-binding modes. Homology models obtained from sequence alignments that discriminate between Class I and Class II P450s are significantly closer to the experimental crystal structures and more closely reproduce known ligand's binding modes, than those obtained using sequence alignments that combine Class I and Class II P450s. The quality of the models is slightly improved by constructing hybrid-structure models that model three of the most variable regions of P450s independently from the rest of the protein: the B region that includes SRS1, the FG region that includes SRS2 and SRS3 and the beta 4 region that includes SRS6.