Role of Arginine 117 in Substrate Recognition by Human Cytochrome P450 2J2

International Journal of Molecular Sciences
Pierre LafiteDaniel Mansuy

Abstract

The influence of Arginine 117 of human cytochrome P450 2J2 in the recognition of ebastine and a series of terfenadone derivatives was studied by site-directed mutagenesis. R117K, R117E, and R117L mutants were produced, and the behavior of these mutants in the hydroxylation of ebastine and terfenadone derivatives was compared to that of wild-type CYP2J2. The data clearly showed the importance of the formation of a hydrogen bond between R117 and the keto group of these substrates. The data were interpreted on the basis of 3D homology models of the mutants and of dynamic docking of the substrates in their active site. These modeling studies also suggested the existence of a R117-E222 salt bridge between helices B' and F that would be important for maintaining the overall folding of CYP2J2.

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Citations

Dec 19, 2020·Scientific Reports·Liang Xu, Liao Y Chen
Jun 15, 2020·Pharmacology & Therapeutics·Aditi DasHannah C Huff
May 28, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jacqueline Wen Hui LeowEric Chun Yong Chan
Jun 24, 2021·Drug Discovery Today·David MachalzGerhard Wolber

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Methods Mentioned

BETA
protein folding
Assay

Software Mentioned

Pymol
antechamber
NAMD2

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