Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases

Lang, Dorothy M.; Zemla, A. T.; Zhou, C. L. Ecale

The conserved residues of Motif A (in PV, D233 and D238) control the function of the metal ions at the active site (41, 43) , which perform the phosphotransfer essential to polymerase activity (41) . D233 is ligand to the metal (44) . D238 is essential to NTP binding (3). Similar functions for the residues of Motif A have been identified for HCV (45) , HRV (45) and FMDV (2) . Motif A is centered within a spring-like homomorph ( Figure 4B -D). Each end terminates at the exterior surface of the protein, and the beginning and end of the homomorph terminate nearly opposite each other. Mutations in the N-terminal segment of the homomorph (in PV at E226A/E227A) result in small plaques (37) , suggesting that these residues influence the rate of catalysis. This is the region where species-specific structures protrude from the homomorph (PV L224-L229). This position, relative to the conserved motif, is analogous to a similar structure in hmG and Motif F2. All these structures contain a segment that varies in length and composition by species and is located upstream from a highly conserved motif, essential to replication.