Exploring CYP1A1 as anticancer target: homology modeling and in silico inhibitor design

Abstract

Microsomal cytochrome P450 family 1 enzymes has great importance in the bioactivation of mutagens. P450 catalyzed reactions involve a wide range of substrates, and this versatality is reflected in a structural diversity, evident in the active sites of available P450 structures. This structure offers a template to study further structure-function relationships of alternative substrates and other cytochrome P450 family 1 members. In this paper, we document a homology model of CYP P450 1A1 from Homo sapiens, developed on the basis of template crystal structure of human microsomal P450 1a2 in complex with inhibitor (PDB Id: 2HI4). Homology modeling is performed at the programs, both in the commercial and public realms. We tried to explore CYP1A1 as a potential target for anticancer chemotherapy. To gain an insight into the binding of ligands with enzyme, protein-ligand complex was developed by including information about the known ligand as spatial restraints and optimizing the mutual interactions between the ligand and the binding site. Active site characterization and the study for involvement of specific aminoacids in binding with ligand, facilitates structure based inhibitor design. This study should prove useful in the design and development of potential novel anticancer agents.