Development of models for Cytochrome P450 2A5 as well as two of its mutants
It is known that small changes in the amino acid sequence can change the catalytic activity of cytochromes towards substrates dramatically. With the aim to broaden our knowledge about the structural properties of cytochromes and their relation with substrate specificity a model of CYP2A5
was built by homology modelling based on the crystal structure of CYP2C5. Model stability was evaluated by subjection of the model to a free molecular dynamics simulation in a waterbox under almost physiological conditions using the GROMACS program. The protein folding remains stable over
1.5 ns under these conditions. The modelling procedure was repeated for two mutated forms of CYP2A5 with known differing substrate selectivities towards corticosterone and desoxycorticosterone. A detailed analysis of the models and their behaviour in long running molecular dynamics simulations
allows an understanding of the requirements for enzyme activity as well as an explanation of respective experimental data on the molecular level.
Document Type: Research Article
Affiliations: 1: Department of Pharmacy, Institute of Pharmaceutical Chemistry, Heinrich Heine-University, Düsseldorf, Germany 2: Department of Pharmacy, Institute of Pharmaceutical Chemistry, Heinrich Heine-University, Universitätsstr. 1, Düsseldorf, D-40225, Germany, Email: [email protected]
Publication date: 01 April 2005
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