Structural analysis of zinc-finger (TTK) + [Cu(BPA)]2+ /[Cu(IDB)]2+ + DNA complexes: an investigation by molecular dynamics simulation.
In the present study, the molecular dynamics simulation technique is employed to investigate the hydrogen abstraction possibility from sugar of DNA in two designed complexes of copper-based chemical nuclease [Cu(BPA)](2+) bis(2-pyridylmethyl) amine (BPA) or [Cu(IDB)](2+) N,N-bis(2-benzimidazolylmethyl) amine (IDB) bound to the zinc finger protein Tramtrack (TTK). The simulated results show that each of the designed complexes can form a stable conformation within 30 ns of simulation time with the substrate OOH(-) and an 18-base pair (bp) DNA segment and is located in the major groove of the DNA segment. The active terminal O atom of the OOH(-) substrate is found in close proximity to the target C2'H, C3'H, C4'H or C5'H proton of the DNA in TTK + [Cu(BPA)OOH](+) + DNA or TTK + [Cu(IDB)OOH](+) + DNA complex, which is crucial to propose the hydrogen abstraction possibility that is responsible for the DNA cleavage. The positions of copper-based chemical nucleases bound to TTK may substantially influence the hydrogen abstraction possibility. The structures and sizes of ligands in copper-based nucleases are also found to have influence on the order of difficulty of the hydrogen abstraction from the sugars of DNA.
College of Chemistry, Beijing Normal University, Beijing, 100875, China.
Yaru
Y
Wang
Yanyan
Y
Zhu
Yan
Y
Wang
Guangju
G
Chen
D000818:Animals; D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D003851:Deoxyribonucleases / Q000138:chemical synthesis* / Q000737:chemistry; D003855:Deoxyribose / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry*; D016335:Zinc Fingers
D029721:Drosophila Proteins; D012097:Repressor Proteins; C075878:ttk protein, Drosophila; D003855:Deoxyribose; D003300:Copper; D006859:Hydrogen; D004247:DNA; D003851:Deoxyribonucleases