fig2

Figure 2. Human Tdp1 electrostatic surface distribution. Electrostatic surface potential of human Tdp1 is shown in a gradient from negative (red) through neutral (white) to positive (blue) and was degenerated by PyMol. Shown in cyan is the DNA and in green the Topo1-peptide fragment that is bonded to the DNA via phosphate. In the used structure, the phosphate was replaced by a vanadate to capture the Tdp1-Topo1-DNA complex (PDB file: 1NOP Davies 2003). A positively charged “DNA-gorge/cleft” fits single strand DNA with the adducted end located in the catalytic pocket from which a “funnel cone” shape pocket emerges that facilitates docking of the protein/peptide adduct. The yellow zoom box highlights the electrostatic charge distribution of the DNA-gorge, catalytic pocket, and funnel cone in which a potential inhibitor will need to bind to prevent Tdp1 interaction with and hydrolyzes of a DNA-adduct. The figure was generated using MacPyMol (DeLano Scientific, San Carlos CA). Topo1: topoisomerase I; Tdp1: tyrosyl-DNA phosphodiesterase I