Linked Life Data

9572842

Source:http://linkedlifedata.com/resource/pubmed/id/9572842

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1998-6-8
pubmed:databankReference
pubmed:abstractText
Nucleoside N-ribohydrolases are targets for disruption of purine salvage in the protozoan parasites. The structure of a trypanosomal N-ribohydrolase in complex with a transition-state inhibitor is reported at 2.3 A resolution. The nonspecific nucleoside hydrolase from Crithidia fasciculata cocrystallized with p-aminophenyliminoribitol reveals tightly bound Ca2+ as a catalytic site ligand. The complex with the transition-state inhibitor is characterized by (1) large protein conformational changes to create a hydrophobic leaving group site (2) C3'-exo geometry for the inhibitor, typical of a ribooxocarbenium ion (3) stabilization of the ribooxocarbenium analogue between the neighboring group 5'-hydroxyl and bidentate hydrogen bonds to Asn168; and (4) octacoordinate Ca2+ orients a catalytic site water and is liganded to two hydroxyls of the inhibitor. The mechanism is ribooxocarbenium stabilization with weak leaving group activation and is a departure from glucohydrolases which use paired carboxylates to achieve the transition state.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6277-85
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
pubmed:affiliation
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't