DIANA LARISA VLĂDOIU*, CRISTINA BEJINAR*, DENISA VOICULESCU*, A. KOLOZSVARI*, DANIELA DATCU*, A. CIORSAC**, ADRIANA ISVORAN*#
*Department of Biology-Chemistry and Advanced Environmental Research Laboratories, West University of Timișoara, Romania
** Department of Physical Education and Sport, Politehnica University of Timișoara, 2 P-ța Victoriei, 300306 Timișoara, Romania
Cytochrome P450 enzymes (CYPs) are involved in phase I of metabolism of many xenobiotics, including drugs. The CYPs belonging to the family 2 are known to be responsible for about 20% of the total drugs metabolism and it underlines the importance of understanding the structural properties of these enzymes in correlation with their biological functions. This paper compares structural properties of the members of subfamily 2C of the human cytochrome P450: CYP2C8, CYP2C9 and CYP2C19. It also analyzes the effects of point mutations corresponding to polymorphic variants of these enzymes on the local hydrophobicity and flexibility of the proteins chains. The three enzymes share high sequence identities, similar global physicochemical properties and a high resemblance of their global spatial structures. Despite their global structural similarity, there are local conformational differences concerning the binding sites with direct consequences on the specificity of every enzyme. The genetic polymorphism of the cytochromes belonging to the subfamily 2C is reflected by some amino acid mutations that significantly affect the local hydrophobicity and/or flexibility of the proteins chains and resulting in their poor ability to metabolize some drug or prodrug compounds.
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