Molecular interaction analysis of cigarette smoke carcinogens NNK and NNAL with enzymes involved in DNA repair pathways: An in silico approach



Qazi Mohd Sajid Jamal1, Mohtashim Lohani1, Mohd Haris Siddiqui1, Mohd Haneef1, Shailendra Kumar Gupta2 & Gulshan Wadhwa3*



1Department of Biotechnology, Microbiology and Bioinformatics, Integral University, Lucknow-226026, India; 2System Toxicology Group, CSIR-Indian Institute of Toxicology Research, PO Box - 80, MG Marg, Lucknow-226001, India; 3Department of Biotechnology, Ministry of Science and Technology, CGO complex, Lodhi Road, New Delhi-110 003, India.


Email; *Corresponding author


Article Type




Received August 08, 2012; Accepted August 20, 2012; Published September 11, 2012



DNA damage occurs almost all the times in cells, but is repaired also continuously. Occurrence of all these mutations and their accumulation in one cell which finally becomes tumorigenic/carcinogenic appears possible if the DNA repair mechanism is hampered. We hypothesize that alterations in DNA repair pathways, either all or at least at one i.e. genetic, translational or post-translational level, becomes quite imperative for the initiation and progression of Cancer. Therefore, we investigated the interaction capability of some carcinogens with the enzymes involved in the DNA repair mechanisms. Cigarette smoke’s derivatives like NNK and NNAL are well established carcinogens. Hence, we analyzed 72 enzymes involved in the DNA repair Mechanisms for their interactions with ligands (NNK and NNAL). The binding efficiencies with enzymes ranging from +36.96 to -7.47 Kcal/Mol. Crystal Structure of Human Carbonmonoxy-Haemoglobin at 1.25 Ĺ Resolution, PDB ID-1IRD as a +Ve control, showed binding energy -6.31 to -6.68 Kcal/Mol. and Human heat shock factor-binding protein 1, PDB ID- 3CI9 as a -Ve control, showed -3.91 to +2.09 Kcal/Mol. Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. Study indicated the loss of functions of these enzymes, which probably could be a reason for fettering of DNA repair pathways resulting in damage accumulation and finally cancer formation.



Cancer, DNA damage and repair, NNK, NNAL, Molecular docking



Jamal et al. Bioinformation 8(17): 795-800 (2012)





Biomedical Informatics



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