The xylose reductase (AKR2B5) structure: homology and divergence from other aldo-keto reductases and opportunities for protein engineering.
The structure of xylose reductase from Candida tenuis (AKR2B5) has been determined and refined to 2.2 A resolution, both in holo and apo forms. These structures allow the recognition of numerous hydrophilic residues responsible for dimerization, a novel feature for the superfamily of enzymes. The residues allowing for dual NADH/NADPH cosubstrate specificity are also identified. Since xylose reductase functions in conjunction with an NAD(+)-specific xylitol dehydrogenase in the xylose assimilation pathway, this is a key step in engineering an enzyme specific for only NADH which will permit cosubstrate recycling between the two enzymes in a high-flux pathway. The structure of xylose reductase, combined with others in the superfamily provides an opportunity to examine and compare structural divergence as a function of sequence homology. It also suggests that the dimeric aldo-keto reductases (AKRs) from families 2 and 7 evolved from a common dimeric ancestor.
Wilson
David K
DK
Section of Molecular and Cellular Biology, University of California, One Shields Avenue, Davis, CA 95616, USA. dave@alanine.ucdavis.edu
Kavanagh
Kathryn L
KL
Klimacek
Mario
M
Nidetzky
Bernd
B
D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D000449:Aldehyde Reductase / Q000737:chemistry* / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D019281:Dimerization; D008958:Models, Molecular; D011487:Protein Conformation; D015202:Protein Engineering
D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase