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Figure 6.
Figure 6. (a) R = OdTDP. A possible mechanism for RmlC based
on structural and biochemical data. The key active site residues
are shown, the H65 is the catalytic base for both
epimerizations, K73 stabilizes the enolate and Y134 acts as the
acid for the first epimerization. The mono-epimerized
intermediate is shown boxed and has the equatorial linkage
between carbohydrate ring and nucleotide. It cannot proceed
directly to product because the C3′ proton is only
sufficiently acidic when it is orthogonal to the plane of the
carbonyl function. (b) R = OdTDP. An alternative route for the
first epimerization using a twist boat form of substrate, the
mono epimerized intermediate is shown boxed. The apparent
preference of RmlC for the equatorial linked sugar nucleotide
suggests that this is a possibility.
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