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

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Title	*Molecular interaction analysis of cigarette smoke carcinogens NNK and NNAL with enzymes involved in DNA repair pathways: An in silico* approach**
Authors	Qazi Mohd Sajid Jamal¹, Mohtashim Lohani¹, Mohd Haris Siddiqui¹, Mohd Haneef¹, Shailendra Kumar Gupta² & Gulshan Wadhwa³*
Affiliation	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	gulshan.dbt@nic.in; *Corresponding author
Article Type	Hypothesis
Date	Received August 08, 2012; Accepted August 20, 2012; Published September 11, 2012
Abstract	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 Å 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.
Keywords	Cancer, DNA damage and repair, NNK, NNAL, Molecular docking
Citation	Jamal et al. Bioinformation 8(17): 795-800 (2012)
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.