Abstract
The crystal structure of the GCY1 gene product from Saccharomyces cerevisiae has been determined to 2.5 Å and is being refined. The model includes two protein molecules, one apo and one holo, per asymmetric unit. Examination of the model reveals that the active site surface is somewhat flat when compared with the other aldo-keto reductase structures, possibly accommodating larger substrates. The Km for NADPH (28.5 μM) is higher than that seen for other family members. This can be explained structurally by the lack of the 'safety belt' of residues seen in other aldo-keto reductases with higher affinity for NADPH. Catalysis also differs from the other aldo-keto reductases. The tyrosine that acts as an acid in the reduction reaction is flipped out of the catalytic pocket. This implies that the protein must either undergo a conformational change before catalysis can take place or that there is an alternate acid moiety.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 527-536 |
| Number of pages | 10 |
| Journal | Chemico-Biological Interactions |
| Volume | 130-132 |
| DOIs | |
| State | Published - Jan 30 2001 |
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Keywords
- Aldo-keto reductase
- Crystal structure
- Gcy1p
ASJC Scopus subject areas
- Toxicology
Cite this
The crystal structure of the GCY1 protein from S. cerevisiae suggests a divergent aldo-keto reductase catalytic mechanism. / Hur, Eugene; Wilson, David K.
In: Chemico-Biological Interactions, Vol. 130-132, 30.01.2001, p. 527-536.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The crystal structure of the GCY1 protein from S. cerevisiae suggests a divergent aldo-keto reductase catalytic mechanism
AU - Hur, Eugene
AU - Wilson, David K.
PY - 2001/1/30
Y1 - 2001/1/30
N2 - The crystal structure of the GCY1 gene product from Saccharomyces cerevisiae has been determined to 2.5 Å and is being refined. The model includes two protein molecules, one apo and one holo, per asymmetric unit. Examination of the model reveals that the active site surface is somewhat flat when compared with the other aldo-keto reductase structures, possibly accommodating larger substrates. The Km for NADPH (28.5 μM) is higher than that seen for other family members. This can be explained structurally by the lack of the 'safety belt' of residues seen in other aldo-keto reductases with higher affinity for NADPH. Catalysis also differs from the other aldo-keto reductases. The tyrosine that acts as an acid in the reduction reaction is flipped out of the catalytic pocket. This implies that the protein must either undergo a conformational change before catalysis can take place or that there is an alternate acid moiety.
AB - The crystal structure of the GCY1 gene product from Saccharomyces cerevisiae has been determined to 2.5 Å and is being refined. The model includes two protein molecules, one apo and one holo, per asymmetric unit. Examination of the model reveals that the active site surface is somewhat flat when compared with the other aldo-keto reductase structures, possibly accommodating larger substrates. The Km for NADPH (28.5 μM) is higher than that seen for other family members. This can be explained structurally by the lack of the 'safety belt' of residues seen in other aldo-keto reductases with higher affinity for NADPH. Catalysis also differs from the other aldo-keto reductases. The tyrosine that acts as an acid in the reduction reaction is flipped out of the catalytic pocket. This implies that the protein must either undergo a conformational change before catalysis can take place or that there is an alternate acid moiety.
KW - Aldo-keto reductase
KW - Crystal structure
KW - Gcy1p
UR - http://www.scopus.com/inward/record.url?scp=0035969879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035969879&partnerID=8YFLogxK
U2 - 10.1016/S0009-2797(00)00296-9
DO - 10.1016/S0009-2797(00)00296-9
M3 - Article
C2 - 11306072
AN - SCOPUS:0035969879
VL - 130-132
SP - 527
EP - 536
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
SN - 0009-2797
ER -