title: Binding Pattern Elucidation of NNK and NNAL Cigarette Smoke Carcinogens with NER Pathway Enzymes: an Onco- Informatics Study.
abstract: Cigarette smoke derivatives like NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol) are well-known carcinogens. We analyzed the interaction of enzymes involved in the NER (nucleotide excision repair) pathway with ligands (NNK and NNAL). Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. The highest obtained docking energy between NNK and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.13 kcal/mol, -7.27 kcal/mol, -8.05 kcal/mol and -7.58 kcal/mol respectively. Similarly the highest obtained docking energy between NNAL and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.46 kcal/mol, -7.94 kcal/mol, -7.83 kcal/mol and -7.67 kcal/mol respectively. In order to find out the effect of NNK and NNAL on enzymes involved in the NER pathway applying protein-protein interaction and protein-complex (i.e. enzymes docked with NNK/NNAL) interaction analysis. It was found that carcinogens are well capable to reduce the normal functioning of genes like RAD23A (HR23A), CCNH, CDK7 and CETN2. In silico analysis indicated loss of functions of these genes and their corresponding enzymes, which possibly might be a cause for alteration of DNA repair pathways leading to damage buildup and finally contributing to cancer formation.
authors.affiliation: Department of Health Information Management, College of Applied Medical Sciences, Buraydah Colleges, Al-Qassim-Buraydah King Abdulaziz Road, East Qassim University, Buraydah, Saudi Arabia E-mail : mlohani@iul.ac.in.
authors.forename: Qazi Mohammad Sajid
authors.initials: QM
authors.lastname: Jamal
authors.forename: Anupam
authors.initials: A
authors.lastname: Dhasmana
authors.forename: Mohtashim
authors.initials: M
authors.lastname: Lohani
authors.forename: Sumbul
authors.initials: S
authors.lastname: Firdaus
authors.forename: Md Yousuf
authors.initials: MY
authors.lastname: Ansari
authors.forename: Ganesh Chandra
authors.initials: GC
authors.lastname: Sahoo
authors.forename: Shafiul
authors.initials: S
authors.lastname: Haque
mesh_terms: D000465:Algorithms; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D002273:Carcinogens / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology / Q000379:methods; D056748:Cyclin H / Q000737:chemistry / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009602:Nitrosamines / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D012907:Smoking; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: C534751:CCNH protein, human; C472752:CETN2 protein, human; D002135:Calcium-Binding Proteins; D002273:Carcinogens; D018797:Cell Cycle Proteins; D056748:Cyclin H; D004268:DNA-Binding Proteins; D009602:Nitrosamines; D011725:Pyridines; C086985:RAD23A protein, human; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D018844:Cyclin-Dependent Kinases; D045643:DNA Repair Enzymes; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human