Exploring structurally conservative blocks as universal templates for modeling eukaryotic cytochrome P450s.

Background: An increasing number of crystal structures for eukaryotic P450s have been published, which provided the chance to explore more structural features and construct some knowledge-based methods to facilitate modeling.

Methods: The crystal structures of 14 cytochrome P450s (CYP450) were selected to extract generic spatial anchors typical for three-dimensional (3D) structures of eukaryotic P450s. Multiple sequence alignment and structural superimposition were applied to recognize evolutionarily conserved regions.

Results: Regions containing uninterrupted helical components were identified as structurally conservative blocks (SCBs). The reliability and robustness of the SCBs were further evaluated by sequence entropy and structural deviation. Finally, these SCBs were applied and tested directly in constructing the homology model of the P450 1B1.

Conclusions: SCBs could potentially be applied as universal template to standardize the homology modeling procedure and help predict drug metabolism preferences for eukaryotic P450s.