Fig. 5.

Structural changes in EFdA-containing complexes. (A) Superposition of N-complex RT/DNA_{EFdA-MP^P•dT-MP^N} and ternary complex RT/DNA_ddG-MP^P/EFdA-TP (magenta DNA). (B) Superposition of two N complexes of RT, in the presence or absence of EFdA-MP at the P site [RT/DNA_{EFdA-MP^P•dT-MP^N} and RT/DNA_{dA-MP^P•AZT-MP^N} (PDB ID 1N6Q in light brown) (17)]. In both A and B, without the localized 1.6-Å primer shift (marked dotted arrow) of EFdA-MP^P, the currently observed 3.3-Å distance between the 4′-E and main-chain carbonyl of Y183 would have been highly unfavorable at ∼1.7 Å. This shift is accomplished through a change in the γ-torsion angle about the C4′-C5′ (Fig. S6A vs. Fig. S6B; Table S1). (C) Primer distortion due to interactions of P-site EFdA-MP of RT/DNA_{EFdA-MP^P•EFdA-MP^N} with Y183 (red arrow) compared with RT/DNA_ddG-MP^P/EFdA-TP (magenta DNA); hydrophobic interactions of the 4′-E at the active-site hydrophobic pocket (red dotted lines connect atoms within 4 Å). (D) The change in γ results in increased distance between neighboring phosphates near the polymerase active site.