FIG 4.

Identification of the putative inhibitor binding site on the structure of PFV RNase H. The normalized chemical shift changes (weighted geometric average of ¹H^N and ¹⁵N chemical shift changes) are shown in the PFV RNase H. Amino acids showing significant chemical shift changes at an RDS1643 concentration of 3.9 mM are highlighted. Changes of ≥0.02 ppm are illustrated in pink, changes of >0.03 ppm are shown in violet, and changes of >0.04 ppm are shown in red. The active-site residues are represented in green. (A) Ribbon presentation of PFV RNase H (PDB ID 2LSN). (B) Surface presentation of PFV RNase H highlighting the surface-exposed residues with significant chemical shift changes. (C) Surface presentation of PFV RNase H with an RNA/DNA hybrid. Based on the structure of the human RNase H-substrate complex (PDB ID 2QK9), a structural alignment of the PFV and human RNase H was performed to model the RNA/DNA substrate of the human RNase H onto PFV RNase H (root mean square deviation [RMSD], 2.35 Å) (8). The RNA strand is shown in dark blue and the DNA strand in light blue. (D) Inhibitor modeling. RDS1643 was modeled onto the structure of the PFV RNase H using the modeling program AutoDock Vina (29).