Structural analysis of zinc-finger (TTK) + [Cu(BPA)]2+ /[Cu(IDB)]2+ + DNA complexes: an investigation by molecular...

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.