Abstract
Cytochrome P450 is a focus of attention as it comprises one of the largest superfamilies of enzyme proteins. Metabolization of many drugs is affected by cytochrome P450. It is an attractive drug target, e.g., cytochrome P450s of Mycobacterium tuberculosis are promising targets in the fight against tuberculosis. The structure provides new insights for investigation of structure/mechanism of cytochrome P450, and for rational design of inhibitor molecules. We will illustrate how biocomputing and bioinformatical techniques reveal details, functions and further secrets of this exciting molecule. Molecular modelling along with site-directed mutagenesis of P450 2B1 elucidated the molecular determinants of substrate specifity. Regioselectivity of progesterone hydroxylation by cytochrome P450 2B1 was reengineered based on the X-ray structure of cytochrome 2C5. Docking approaches rationalized the regioselectivity of the reengineered cytochrome P450 2B1. Furthermore, by methods of molecular dynamic simulations, routes were identified by which substrates may enter into and products exit from the active site of cytochrome P450.
Keywords
- Molecular Dynamic Simulation
- Active Site Residue
- Steer Molecular Dynamic
- Stereochemical Quality
- Curr Opin Struct Biol
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Schleinkofer, K., Dandekar, T. (2006). Clues from Three-Dimensional Structure Analysis and Molecular Modelling. In: Discovering Biomolecular Mechanisms with Computational Biology. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-36747-0_3
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DOI: https://doi.org/10.1007/0-387-36747-0_3
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