Abstract
The structure of xylose reductase from Candida tenuis (AKR2B5) has been determined and refined to 2.2 Å 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 515-521 |
| Number of pages | 7 |
| Journal | Chemico-Biological Interactions |
| Volume | 143-144 |
| DOIs | |
| State | Published - Feb 1 2003 |
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Keywords
- Candida tenuis
- Engineering
- Homology
ASJC Scopus subject areas
- Toxicology
Cite this
The xylose reductase (AKR2B5) structure : Homology and divergence from other aldo-keto reductases and opportunities for protein engineering. / Wilson, David K.; Kavanagh, Kathryn L.; Klimacek, Mario; Nidetzky, Bernd.
In: Chemico-Biological Interactions, Vol. 143-144, 01.02.2003, p. 515-521.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The xylose reductase (AKR2B5) structure
T2 - Homology and divergence from other aldo-keto reductases and opportunities for protein engineering
AU - Wilson, David K.
AU - Kavanagh, Kathryn L.
AU - Klimacek, Mario
AU - Nidetzky, Bernd
PY - 2003/2/1
Y1 - 2003/2/1
N2 - The structure of xylose reductase from Candida tenuis (AKR2B5) has been determined and refined to 2.2 Å 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.
AB - The structure of xylose reductase from Candida tenuis (AKR2B5) has been determined and refined to 2.2 Å 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.
KW - Candida tenuis
KW - Engineering
KW - Homology
UR - http://www.scopus.com/inward/record.url?scp=0037324956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037324956&partnerID=8YFLogxK
U2 - 10.1016/S0009-2797(02)00211-9
DO - 10.1016/S0009-2797(02)00211-9
M3 - Article
VL - 143-144
SP - 515
EP - 521
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
SN - 0009-2797
ER -