Linked Life Data

12269808

Source:http://linkedlifedata.com/resource/pubmed/id/12269808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2002-9-24
pubmed:abstractText
Few techniques for probing the role of individual amino acids in interactions of a protein with ligands are available. Chemical shift perturbations in NMR spectra provide qualitative information about the response of individual amino acids of a protein to its interactions with ligands. Line shapes derived from (15)N-HSQC spectra recorded for different steps of a ligand titration yield both kinetic constants and insight into mechanisms by which the ligand binds. Here we have analyzed line shapes for 37 signals of amino acids of the N-terminal src homology 2 domain (N-SH2) of the 85 kDa subunit of phosphatidylinositol 3-kinase (PI3-K) upon binding of phosphotyrosine (ptyr)-containing peptides. Kinetic rates at individual amino acids of the SH2 varied throughout the structure. For a subset of SH2 residues, the fine structure of the NMR line shapes indicated slow motions induced by the presence of small amounts of the ligand. These complex line shapes require one or more additional conformational states on the kinetic pathway. Modeling of the observed ligand interactions suggests a quasi-allosteric initial binding step. N-SH2 mutants with altered ligand affinity or specificity were also examined. Analysis of their line shapes revealed three distinct classes of mutants with different kinetic behaviors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11658-69
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Probing Src homology 2 domain ligand interactions by differential line broadening.
pubmed:affiliation
Institute of Biophysical Chemistry, J. W. Goethe University, Frankfurt, Biocenter N230, Marie-Curie-Strasse 9, 60439 Frankfurt, Germany. ugunt@bpc.uni-frankfurt.de
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't