|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
13
|
|
pubmed:dateCreated |
2004-3-22
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
Escherichia coli YiaK catalyzes the reduction of 2,3-diketo-L-gulonate in the presence of NADH. It belongs to a large family of oxidoreductases that is conserved in archaea, bacteria, and eukaryotes but shows no sequence homology to other proteins. We report here the crystal structures at up to 2.0-A resolution of YiaK alone and in complex with NAD-tartrate. YiaK has a new polypeptide backbone fold and a novel mode of recognizing the NAD cofactor. In addition, NAD is bound in an unusual conformation, at the interface of a dimer of the enzyme. The crystallographic analysis unexpectedly revealed the binding of tartrate in the active site. Enzyme kinetics studies confirm that tartrate and the related D-malate are inhibitors of YiaK. In contrast to most other enzymes where substrate binding produces a more closed conformation, the binding of NAD-tartrate to YiaK produces a more open active site. The free enzyme conformation is incompatible with NAD binding. His(44) is likely the catalytic residue of the enzyme.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
26
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
13148-55
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:14718529-Amino Acid Sequence,
pubmed-meshheading:14718529-Binding Sites,
pubmed-meshheading:14718529-Catalytic Domain,
pubmed-meshheading:14718529-Crystallography, X-Ray,
pubmed-meshheading:14718529-Dimerization,
pubmed-meshheading:14718529-Electrons,
pubmed-meshheading:14718529-Escherichia coli,
pubmed-meshheading:14718529-Escherichia coli Proteins,
pubmed-meshheading:14718529-Kinetics,
pubmed-meshheading:14718529-Models, Chemical,
pubmed-meshheading:14718529-Models, Molecular,
pubmed-meshheading:14718529-Molecular Sequence Data,
pubmed-meshheading:14718529-NAD,
pubmed-meshheading:14718529-Protein Binding,
pubmed-meshheading:14718529-Protein Conformation,
pubmed-meshheading:14718529-Protein Structure, Tertiary,
pubmed-meshheading:14718529-Sequence Homology, Amino Acid,
pubmed-meshheading:14718529-Sugar Acids,
pubmed-meshheading:14718529-Sugar Alcohol Dehydrogenases,
pubmed-meshheading:14718529-Tartrates
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
A novel NAD-binding protein revealed by the crystal structure of 2,3-diketo-L-gulonate reductase (YiaK).
|
|
pubmed:affiliation |
Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY 10027, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
