Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2005-4-4
pubmed:databankReference
pubmed:abstractText
The post-translational farnesylation of proteins serves to anchor a subset of intracellular proteins to membranes in eukaryotic organisms and also promotes protein-protein interactions. Inhibition of protein farnesyltransferase (PFT) is lethal to the pathogenic protozoa Plasmodium falciparum. Parasites were isolated that were resistant to BMS-388891, a tetrahydroquinoline (THQ) PFT inhibitor. Resistance was associated with a 12-fold decrease in drug susceptibility. Genotypic analysis revealed a single point mutation in the beta subunit in resistant parasites. The resultant tyrosine 837 to cysteine alteration in the beta subunit corresponded to the binding site for the THQ and peptide substrate. Biochemical analysis of Y837C-PFT demonstrated a 13-fold increase in BMS-388891 concentration necessary for inhibiting 50% of the enzyme activity. These data are consistent with PFT as the target of BMS-388891 in P. falciparum and suggest that PFT inhibitors should be combined with other antimalarial agents for effective therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13554-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15661734-Alkyl and Aryl Transferases, pubmed-meshheading:15661734-Amino Acid Sequence, pubmed-meshheading:15661734-Animals, pubmed-meshheading:15661734-Binding Sites, pubmed-meshheading:15661734-Drug Resistance, pubmed-meshheading:15661734-Humans, pubmed-meshheading:15661734-Imidazoles, pubmed-meshheading:15661734-Malaria, pubmed-meshheading:15661734-Models, Molecular, pubmed-meshheading:15661734-Molecular Sequence Data, pubmed-meshheading:15661734-Molecular Structure, pubmed-meshheading:15661734-Plasmodium falciparum, pubmed-meshheading:15661734-Point Mutation, pubmed-meshheading:15661734-Protein Processing, Post-Translational, pubmed-meshheading:15661734-Protein Subunits, pubmed-meshheading:15661734-Protozoan Proteins, pubmed-meshheading:15661734-Quinolines, pubmed-meshheading:15661734-Sequence Alignment
pubmed:year
2005
pubmed:articleTitle
Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum.
pubmed:affiliation
Department of Pathobiology, University of Washington, Seattle, Washington 98195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural