Linked Life Data

10760841

Source:http://linkedlifedata.com/resource/pubmed/id/10760841

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2000-6-30
pubmed:abstractText
Computer-assisted molecular modelling was used to generate structures for the trimethoprim (TMP):NADPH:dihydrofolate reductase (DHFR) ternary complexes for human wild-type DHFR and for five DHFR mutants (L22R, L22F, F31S, F31W and Q35P). The mutants correspond to DHFR proteins that have been isolated from tissues exposed to chronic or high dose methotrexate (MTX) and show decreased sensitivity to antifolate inhibition. Analysis of the TMP:DHFR interactions suggest the presence of two subsets of TMP binding residues in the DHFR antifolate binding site. One subset of these residues (GLU30, PHE34, ILE60 and VAL115) are common to each DHFR complex studied and are referred to as core residues. The other TMP binding residues vary among the DHFR complexes studied and are referred to as noncore residues. The core residues exhibit a greater number of TMP contacts/residue and form more stable TMP interactions than noncore residues. Additionally, the core and noncore residues make contact with different regions of the TMP structure. Information presented here provides additional insight into the design of new agents for the improved inhibition of wild-type DHFR and the simultaneous inhibition of both wild-type and mutant DHFR molecules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0142-2782
pubmed:author
pubmed:copyrightInfo
Copyright 1999 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
335-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Molecular modelling of trimethoprim complexes of human wild-type and mutant dihydrofolate reductases: identification of two subsets of binding residues in the antifolate binding site.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC 20059, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.