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Analysis of Species-Selectivity of Human, Mouse and Rat Cytochrome P450 1A and 2B Subfamily Enzymes using Molecular Modeling, Docking and Dynamics Simulations.

Authors
  • Karthikeyan, Bagavathy Shanmugam1, 2
  • Suvaithenamudhan, Suvaiyarasan1
  • Akbarsha, Mohammad Abdulkader2
  • Parthasarathy, Subbiah3
  • 1 Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620 024, Tamil Nadu, India. , (India)
  • 2 Mahatma Gandhi-Doerenkamp Center (MGDC) for Alternatives to Use of Animals in Life Science Education, Bharathidasan University, Tiruchirappalli, 620 024, Tamil Nadu, India. , (India)
  • 3 Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620 024, Tamil Nadu, India. [email protected] , (India)
Type
Published Article
Journal
Cell Biochemistry and Biophysics
Publisher
Springer-Verlag
Publication Date
Mar 29, 2017
Identifiers
DOI: 10.1007/s12013-017-0791-8
PMID: 28353142
Source
Medline
Keywords
License
Unknown

Abstract

Cytochrome P450 (CYP) 1A and 2B subfamily enzymes are important drug metabolizing enzymes, and are highly conserved across species in terms of sequence homology. However, there are major to minor structural and macromolecular differences which provide for species-selectivity and substrate-selectivity. Therefore, species-selectivity of CYP1A and CYP2B subfamily proteins across human, mouse and rat was analyzed using molecular modeling, docking and dynamics simulations when the chiral molecules quinine and quinidine were used as ligands. The three-dimensional structures of 17 proteins belonging to CYP1A and CYP2B subfamilies of mouse and rat were predicted by adopting homology modeling using the available structures of human CYP1A and CYP2B proteins as templates. Molecular docking and dynamics simulations of quinine and quinidine with CYP1A subfamily proteins revealed the existence of species-selectivity across the three species. On the other hand, in the case of CYP2B subfamily proteins, no role for chirality of quinine and quinidine in forming complexes with CYP2B subfamily proteins of the three species was indicated. Our findings reveal the roles of active site amino acid residues of CYP1A and CYP2B subfamily proteins and provide insights into species-selectivity of these enzymes across human, mouse, and rat.

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