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Figure 5.
Figure 5. Proposed reaction mechanisms of hydride transfer for
HSD. a, Probable reaction mechanism for the forward direction
with the substrate in the aldehyde form. Asp 214, Glu 208 and
Wat460 serve to bind the substrate, whereas Lys 223, oriented by
Asp 219, donates a proton to the C4 oxygen of l-ASA. The
cofactor NADH delivers its pro-S hydride to the C4 carbon of
l-ASA. Arrows indicate electron flow. b, Alternative reaction
mechanism for the forward direction with the substrate in the
gem-diol form. The main difference from the reaction proposed
for the aldehyde form is that Lys 223 donates a proton to the
hydroxyl group, which departs as a water molecule, and Asp 219
hydrogen bonds to the hydroxyl group, which remains in the
product alcohol.
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