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. 2007 May 14;51(8):2920–2928. doi: 10.1128/AAC.00186-07

FIG. 9.

FIG. 9.

Parameters affecting the excision of nonobligate chain terminators. The nucleotide binding site of HCV NS5B is shown in orange (N site [N]), and the priming site is shown in yellow (P site [P]). Natural nucleotides are highlighted in gray, and the nonobligate chain terminator is shown in blue. The methyl group at the 2′ position of the sugar moiety is shown enlarged. (A) Immediately following nucleotide incorporation, the chain terminator still occupies the N site. (B) Excision can occur only in this configuration. (C) Binding of the next nucleotide requires polymerase translocation, which clears the nucleotide binding site. (C′) The methyl group at the 2′ position of the sugar moiety is shown enlarged. The chain terminator is now located in the P site. (D) In this position, binding of the next correct nucleotide blocks the enzyme in a ternary DEC that is catalytically inactive. (D′) Nucleotide binding and DEC formation are severely compromised with 2′-methylated chain terminators.