Linked Life Data

1895291

Source:http://linkedlifedata.com/resource/pubmed/id/1895291

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1991-10-22
pubmed:abstractText
In the continuation of a project aimed at the rational design of drugs against diseases caused by trypanosomes, the crystal structure of trypanosomal triosephosphate isomerase in complex with the active site inhibitor 2-phosphoglycerate has been determined. Two alternative modeling protocols have been attempted to predict the mode of binding of this ligand. In the first protocol, certain key interactions were restrained in the modeling procedure. In the second protocol, a full search of ligand conformational space was performed. In both cases the protein scaffold was kept static. Both protocols produced models which were reasonably close to the observed structure (rms difference less than 2.0 A). Nevertheless, some essential features were missed by each of the protocols. The crystallographic structure of the 2-PGA TIM complex shows that the ligand binds fully within the active site of TIM, with partners for all but one of the ligand's strongly hydrogen bonding groups. Several of the interactions between the ligand and the active site of TIM are seen to be common to all of the complexes so far structurally characterized between trypanosomal triosephosphate isomerase and competitive inhibitors. Such key interactions appear to be the best guide in the prediction of the binding mode of a new inhibitor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2709-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Crystallographic and molecular modeling studies on trypanosomal triosephosphate isomerase: a critical assessment of the predicted and observed structures of the complex with 2-phosphoglycerate.
pubmed:affiliation
European Molecular Biology Laboratory, Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't