Linked Life Data

15533662

Source:http://linkedlifedata.com/resource/pubmed/id/15533662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-11-9
pubmed:abstractText
Plasmon-waveguide resonance (PWR) spectroscopy has been used to study the interactions between ligands that correspond to inhibitors, activators or substrates and three integral membrane proteins representing potential drug targets; cyclooxygenases 1 and 2 (COX-1 and -2), integrin alphaVbeta3, and hepatitis C virus RNA polymerase. The proteins were incorporated into an egg phosphatidylcholine bilayer deposited onto the surface of the PWR resonator, and changes in the amplitude and position of the PWR spectra due to mass density increases and conformational transitions have been used to characterize the kinetics and binding affinities corresponding to these interactions. Although the partition of COX-2 into the bilayer was not as efficient as was the case with the other two proteins, sufficient protein could be incorporated to allow ligand binding to be observed. It was also possible to incorporate COX-1 into a lipid bilayer by adding a suspension of microsomal membrane fragments containing this enzyme to a preformed bilayer, and to observe binding of an inhibitory ligand. The interactions between integrin alphaVbeta3 and two ligands with different in vivo efficacies could be distinguished by both spectral measurements and binding kinetics. In the case of the RNA polymerase, the kinetics of PWR spectral changes upon adding a substrate solution to an enzyme-template complex were consistent with those obtained from direct measurements of enzymatic turnover. These experiments demonstrate the utility of PWR spectroscopy to provide novel information regarding drug interactions with membrane proteins in a lipid environment and to distinguish conformational changes induced by binding of various drug molecules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0731-7085
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
711-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Plasmon-waveguide resonance spectroscopy applied to three potential drug targets: cyclooxygenase-2, hepatitis C virus RNA polymerase and integrin alpha V beta 3.
pubmed:affiliation
Department of Biochemistry and Molecular Biophysics, University of Arizona, Tucson, AZ 85721, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.