Exploring CYP1A1 as anticancer target: homology modeling and in silico inhibitor design |
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Authors: | Abhay T Sangamwar Leena B Labhsetwar Sharad v Kuberkar |
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Institution: | (1) Post Graduate Research Centre, Department of Chemistry, Yeshwant Mahavidyalaya, Nanded, 431605, MS, India;(2) Department of Pharmaceutics, Nanded Pharmacy College, Shyamnagar, Nanded, 431605, MS, India |
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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.
Figure The refined structure of homology model of CYP1A1 |
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Keywords: | Active site CYP1A1 Drug design Homology modeling Protein-ligand complex |
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