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Achary, M.S. and Nagarajaram, H.A. (2008) Comparative docking studies of CYP1b1 and its PCG-associated mutant forms. Journal of Biosciences, 33 (5). pp. 699-713. ISSN 0250-5991

J Biosci 33 p699.pdf

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Molecular docking has been used to compare and contrast the binding modes of oestradiol with the wild-type and some disease-associated mutant forms of the human CYP1b1 protein.The receptor structures used for docking were derived from molecular dynamics simulations of homology-modelled structures. Earlier studies involving molecular dynamics and principal component analysis indicated that mutations could have a disruptive effect on function,by destabilizing the native properties of the functionally important regions, especially those of the haem-binding and substrate-binding regions,which constitute the site of catalytic activity of the enzyme.In order to gain more insights into the possible differences in substrate-binding and catalysis between the wild-type and mutant proteins,molecular docking studies were carried out. Mutants showed altered protein -ligand interactions compared with the wild-type as a consequence of changes in the geometry of the substrate-binding region and in the position of haem relative to the active site. An important difference in ligand -protein interactions between the wild-type and mutants is the presence of stacking interaction with phenyl residues in the wild-type,which is either completely absent or considerably weaker in mutants.The present study revealed essential differences in the interactions between ligand and protein in wild-type and disease mutants,and helped in understanding the deleterious nature of disease mutations at the level of molecular function.

Item Type: Article
Depositing User: Dr P Divakar
Date Deposited: 25 Aug 2015 09:00
Last Modified: 08 Oct 2015 06:18
URI: http://cdfd.sciencecentral.in/id/eprint/376

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