Homology modelling and characterization of three-dimensional (3d) protein structures of selected variants of cyp3a4

Abstract

The efficacy and toxicity of several drugs and prodrugs are influenced by the interindividual genetic variations in drug-metabolising enzymes. Cytochrome P450 enzymes constitute the major metabolising enzymes in humans. Cytochrome 3A4 (CYP3A4) is the highest abundantly expressed human cytochrome P450 enzyme metabolising about 40% of marketed drugs. Several studies have shown the significant effects of CYP3A4 single nucleotide variability on its enzymatic activity and the pharmacokinetic parameters of metabolized drugs. However, there is a paucity of information on the molecular characteristics (including threedimensional protein structures, physicochemical properties, and molecular dynamics characteristics) of single nucleotide variants of CYP3A4 enzymes that may be correlated with the reported variability of their enzymatic activities.