FIGURE 4.

Replacement of the inactivating A-1(2′-O-methyl) modification with the native A-1(2′OH) results in a local, functionally relevant conformational change. (A) Active site geometry of a C39 gain-of-function mutant simulation (color) overlaid with the noncleavable ribozyme-substrate analog complex crystal structure (PDB ID 2OUE, gray) illustrates a change in sugar pucker of A-1 that results in a hydrogen bond from A-1(2′OH) to A38(N1) and hydrogen bonds from G8 to the nonbridging pro-R oxygen (red dashed tubes). (B) The number of simulations that change sugar pucker after a given time (open circles) is well fit with a single-exponential (line).