FIG. 5.

The structure of MK3 bound to the active site of the isolated RNase H domain of RT. (A) MK3 is shown in orange as a space-filling model bound to the active site of RNase H (ribbons). For reference, the two-dimensional representation for the inhibitor is shown on the right. (B) The electron density map (sigmaA weighted 2Fo-Fc map contoured at 1σ) for MK3 bound to RNase H is shown in purple on the left. Binding without the electron density map is shown on the right. The Mn²⁺ ions are shown in green. (C) MK3 from the RNase H domain crystals is overlaid on top of the inhibitors MK1 and MK2 from the full-length RT crystals based on structural alignment of the RNase H domain. The two Mn²⁺ ions, which bind each inhibitor, do not move significantly. The metal-coordinating naphthyridine of MK3 is rotated (left) and tilted out of the plane of MK1 and MK2 (right) due to interactions mediated by the additional benzyl ring.