Role of Residue 90 in Catalysis of Cytochrome P450 2C9

TL;DRAbstract

The cytochrome P450 mutant CYP2C9.13(L90P) shows a greatly impaired catalytic activity compared with the wild-type. We constructed the mutants by substitution at residue 90 of CYP2C9, expressed in COS-7 cells, assayed their thermal stability and catalysis activity and analyzed the mutants via molecular dynamic(MD) simulation and flexible docking. Mutant L90E exhibits a significantly lower catalytic activity than the wild-type for the hydro- xylation of diclofenac, lornoxicam and luciferin and its molecular dynamics simulation results indicate that the size of the entrance of substrate access was reduced significantly. An increase or minor decrease of catalytic activity was observed for mutants L90Q, L90W, L90R, L90I and L90G, and the sizes of the entrances of substrate access and the active site cavities had a little change in those mutants. The thermal stability and the potential energy of the MD si- mulation of these mutants showed a similar tendency as the catalysis assays did. Flex

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