Fig. 3.

Molecular modeling of RNA pol II transcriptional pausing and arrest by Py-Im polyamide. The functional interplay between two critical residues (R1386 and H1387) from the conserved Switch 1 region of Rpb1 and the polyamide-bound minor groove during RNA pol II progression. During translocation, the pol II may move from step i to step iv with distinct steric interactions. In step i, the Py-Im polyamide and these two residues are in positions without obvious steric interaction; in step ii, the polyamide and the residues establish direct contact; in steps iii and iv, strong steric clashes were observed between pol II Switch 1 residues and Py-Im polyamide, and duplex unwinding was also prevented, both of which lead to strong inhibition for RNA pol II elongation complex.