Linked Life Data

15023057

Source:http://linkedlifedata.com/resource/pubmed/id/15023057

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-3-16
pubmed:databankReference
pubmed:abstractText
CDP-D-glucose 4,6-dehydratase catalyzes the conversion of CDP-D-glucose to CDP-4-keto-6-deoxyglucose in an NAD(+)-dependent manner. The product of this conversion is a building block for a variety of primary antigenic determinants in bacteria, possibly implicated directly in reactive arthritis. Here, we describe the solution of the high-resolution crystal structure of CDP-D-glucose 4,6-dehydratase from Yersinia pseudotuberculosis in the resting state. This structure represents the first CDP nucleotide utilizing dehydratase of the short-chain dehydrogenase/reductase (SDR) family to be determined, as well as the first tetrameric structure of the subfamily of SDR enzymes in which NAD(+) undergoes a full reaction cycle. On the basis of a comparison of this structure with structures of homologous enzymes, a chemical mechanism is proposed in which Tyr157 acts as the catalytic base, initiating hydride transfer by abstraction of the proton from the sugar 4'-hydroxyl. Concomitant with the removal of the proton from the 4'-hydroxyl oxygen, the sugar 4'-hydride is transferred to the B face of the NAD(+) cofactor, forming the reduced cofactor and a CDP-4-keto-d-glucose intermediate. A conserved Lys161 most likely acts to position the NAD(+) cofactor so that hydride transfer is favorable and/or to reduce the pK(a) of Tyr157. Following substrate oxidation, we propose that Lys134, acting as a base, would abstract the 5'-hydrogen of CDP-4-keto-D-glucose, priming the intermediate for the spontaneous loss of water. Finally, the resulting Delta(5,6)-glucoseen intermediate would be reduced suprafacially by the cofactor, and reprotonation at C-5' is likely mediated by Lys134.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3057-67
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15023057-Amino Acid Sequence, pubmed-meshheading:15023057-Bacterial Proteins, pubmed-meshheading:15023057-Binding Sites, pubmed-meshheading:15023057-Catalysis, pubmed-meshheading:15023057-Crystallization, pubmed-meshheading:15023057-Crystallography, X-Ray, pubmed-meshheading:15023057-Humans, pubmed-meshheading:15023057-Hydro-Lyases, pubmed-meshheading:15023057-Models, Molecular, pubmed-meshheading:15023057-Molecular Sequence Data, pubmed-meshheading:15023057-NAD, pubmed-meshheading:15023057-Protein Structure, Quaternary, pubmed-meshheading:15023057-Protein Structure, Tertiary, pubmed-meshheading:15023057-Recombinant Proteins, pubmed-meshheading:15023057-Sequence Alignment, pubmed-meshheading:15023057-Sequence Homology, Amino Acid, pubmed-meshheading:15023057-UDPglucose 4-Epimerase, pubmed-meshheading:15023057-Yersinia pseudotuberculosis
pubmed:year
2004
pubmed:articleTitle
Crystal structure at 1.8 A resolution of CDP-D-glucose 4,6-dehydratase from Yersinia pseudotuberculosis.
pubmed:affiliation
Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454-9110, USA. vogan@crystal.harvard.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.