Exploring structurally conservative blocks as universal templates for modeling eukaryotic cytochrome P450s
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Youbin Tu
Abstract
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.
The author would like to thank Xiaolong Zhao for his help with data collection. The work was supported by the start-up fund from Soochow University. Computing and modeling studies were performed at the Structural Bioinformatics Laboratory, School of Basic Medicine and Biological Sciences, Soochow University.
Conflict of interest statement
Author’s conflict of interest disclosure: The author stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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©2012 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Editorial
- Maintain the goals of Drug Metabolism and Drug Interactions
- Reviews
- Cytochrome P450 2B6: function, genetics, and clinical relevance
- In silico pharmacology for a multidisciplinary drug discovery process
- Original Articles
- In vitro effects of three antidepressant drugs on plasma paraoxonase activity
- Development of a HPLC method for the determination of losartan urinary metabolic ratio to be used for the determination of CYP2C9 hydroxylation phenotypes
- Interaction of methocarbamol and yeast sucrase induces enzyme inhibition
- Evaluation of the effect of statin use on the acenocoumarol and phenprocoumon maintenance dose
- Exploring structurally conservative blocks as universal templates for modeling eukaryotic cytochrome P450s
Artikel in diesem Heft
- Masthead
- Masthead
- Editorial
- Maintain the goals of Drug Metabolism and Drug Interactions
- Reviews
- Cytochrome P450 2B6: function, genetics, and clinical relevance
- In silico pharmacology for a multidisciplinary drug discovery process
- Original Articles
- In vitro effects of three antidepressant drugs on plasma paraoxonase activity
- Development of a HPLC method for the determination of losartan urinary metabolic ratio to be used for the determination of CYP2C9 hydroxylation phenotypes
- Interaction of methocarbamol and yeast sucrase induces enzyme inhibition
- Evaluation of the effect of statin use on the acenocoumarol and phenprocoumon maintenance dose
- Exploring structurally conservative blocks as universal templates for modeling eukaryotic cytochrome P450s
