Baudry Jerome, Rupasinghe Sanjeewa, Schuler Mary A
School of Chemical Sciences, University of Illinois at Urbana-Champaign Urbana, IL 61801, USA.
Protein Eng Des Sel. 2006 Aug;19(8):345-53. doi: 10.1093/protein/gzl012. Epub 2006 Jun 15.
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 beta4 region that includes SRS6.
利用与现有P450晶体结构具有不同序列同一性水平的各种序列比对，研究了获取P450同源模型的不同方法。在该分析中，我们研究了同源建模能够多好地再现已知晶体结构，以及这些同源模型能够多有效地用于再现已知配体结合模式。与使用结合I类和II类P450的序列比对所获得的同源模型相比，从区分I类和II类P450的序列比对所获得的同源模型显著更接近实验晶体结构，并且更紧密地再现已知配体的结合模式。通过构建混合结构模型，P450最可变的三个区域独立于蛋白质的其余部分进行建模，从而略微提高了模型的质量：包括SRS1的B区域、包括SRS2和SRS3的FG区域以及包括SRS6的β4区域。
