id author title date pages extension mime words sentences flesch summary cache txt cord-010762-c01wgg4v Wu, Jiqin A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase 2020-05-01 .txt text/plain 9021 382 50 Previously reported NS5 structures represented by those from the Japanese encephalitis virus (JEV) and Dengue virus serotype 3 (DENV3) exhibit two apparently different global conformations, defining two sets of intra-molecular MTase-RdRP interactions. Data from in vitro polymerase assays further demonstrate that perturbing the JEV-mode but not the DENV3-mode intra-molecular interactions inhibits catalysis only at initiation, while the cell-based virological analysis suggests that both modes of interactions are important for virus proliferation. NS5 constructs bearing mutations specifically probing two modes of MTase-RdRP intra-molecular interfaces were tested in in vitro polymerase assays, and only the JEV-mode interface related mutants inhibited polymerase initiation primarily through a three-fold reduction in the Michaelis constant of the initiating NTP (K M, NTP ), while polymerase EC properties were not much affected by mutations probing both modes of interactions. ./cache/cord-010762-c01wgg4v.txt ./txt/cord-010762-c01wgg4v.txt