title: Molecular docking studies of curcumin natural derivatives with DNA topoisomerase I and II-DNA complexes.
abstract: DNA topoisomerase I (topo I) and II (topo II) are essential enzymes that solve the topological problems of DNA by allowing DNA strands or double helices to pass through each other during cellular processes such as replication, transcription, recombination, and chromatin remodeling. Their critical roles make topoisomerases an attractive drug target against cancer. The present molecular docking study provides insights into the inhibition of topo I and II by curcumin natural derivatives. The binding modes suggested that curcumin natural derivatives docked at the site of DNA cleavage parallel to the axis of DNA base pairing. Cyclocurcumin and curcumin sulphate were predicted to be the most potent inhibitors amongst all the curcumin natural derivatives docked. The binding modes of cyclocurcumin and curcumin sulphate were similar to known inhibitors of topo I and II. Residues like Arg364, Asn722 and base A113 (when docked to topo I-DNA complex) and residues Asp479, Gln778 and base T9 (when docked to topo II-DNA complex) seem to play important role in the binding of curcumin natural derivatives at the site of DNA cleavage.
authors.affiliation: Computational Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Utpal
authors.initials: U
authors.lastname: Bora
mesh_terms: D000596:Amino Acids; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001665:Binding Sites; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism*; D053837:DNA Cleavage; D004261:DNA Replication; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D010936:Plant Extracts; D004247:DNA; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; D003474:Curcumin