The crystal structure of the GCY1 protein from S. cerevisiae suggests a divergent aldo-keto reductase catalytic mechanism

Eugene Hur, David K. Wilson

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)527-536
Number of pages10
JournalChemico-Biological Interactions
Volume130-132
DOIs
StatePublished - Jan 30 2001

Fingerprint

Saccharomyces cerevisiae Proteins
Crystal structure
Catalysis
NADP
Acids
Yeast
Saccharomyces cerevisiae
Tyrosine
Catalytic Domain
Proteins
Genes
Safety
Molecules
Substrates
carbonyl reductase (NADPH)

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 journalArticle

@article{3a9564d0948143778b3d14833879e1d9,
title = "The crystal structure of the GCY1 protein from S. cerevisiae suggests a divergent aldo-keto reductase catalytic mechanism",
abstract = "The crystal structure of the GCY1 gene product from Saccharomyces cerevisiae has been determined to 2.5 {\AA} 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.",
keywords = "Aldo-keto reductase, Crystal structure, Gcy1p",
author = "Eugene Hur and Wilson, {David K.}",
year = "2001",
month = "1",
day = "30",
doi = "10.1016/S0009-2797(00)00296-9",
language = "English (US)",
volume = "130-132",
pages = "527--536",
journal = "Chemico-Biological Interactions",
issn = "0009-2797",
publisher = "Elsevier Ireland Ltd",

}

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 -