Structural insight into _D-xylose utilization by xylose reductase from Scheffersomyces stipitis

Lignocellulosic biomass, of which _D-xylose accounts for approximately 35% of the total sugar, has attracted attention as a future energy source for biofuel. To elucidate molecular mechanism of _D-xylose utilization, we determined the crystal structure of _D-xylose reductase from Schefferzomyces stipitis (SsXR) at a 1.95 Å resolution. We also determined the SsXR structure in complex with the NADPH cofactor and revealed that the protein undergoes an open/closed conformation change upon NADPH binding. The substrate binding pocket of SsXR is somewhat hydrophobic, which seems to result in low binding affinity to the substrate. Phylogenetic tree analysis showed that AKR enzymes annotated with bacterial/archaeal XRs belonged to uncharacterized AKR families and might have no XR function, and yeast/fungi derived enzymes, which belong to the same group with SsXR, can be candidates for XR to increase xylose consumption.