Linked Life Data

10548041

Source:http://linkedlifedata.com/resource/pubmed/id/10548041

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-2-11
pubmed:abstractText
We have adopted nanoflow electrospray ionization mass spectrometry (ESI-MS) and isothermal titration calorimetry (ITC) to probe the mechanism of peptide recognition by the SH2 domain from the Src family tyrosine kinase protein, Fyn. This domain is involved in the mediation of intracellular signal transduction pathways by interaction with proteins containing phosphorylated tyrosine (Y*) residues. The binding of tyrosyl phosphopeptides can mimic these interactions. Specificity in these interactions has been attributed to the interaction of the Y* and residues proximal and C-terminal to it. Previous studies have established that for specific binding with Fyn, the recognition sequence consists of pTyr-Glu-Glu-Ile. The specific interactions involve the binding of Y* with the ionic, and the Y* + 3 Ile residue with the hydrophobic binding pockets on the surface of the Fyn SH2 domain. In this work, a variation in the Y* + 3 residue of this high-affinity sequence was observed to result in changes in the relative binding affinities as determined in solution (ITC) and in the gas phase (nanoflow ESI-MS). X-ray analysis shows that a feature of the Src family SH2 domains is the involvement of water molecules in the peptide binding site. Under the nanoflow ESI conditions, water molecules appear to be maintained in the Fyn SH2-ligand complex. Compelling evidence for these molecules being incorporated in the SH2-peptide interface is provided by the prevalence of the peaks assigned to water-bound over the water-free complex at high-energy conditions. Thus, the stability of water protein-ligand complex appears to be intimately linked to the presence of water.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-1379696, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-1709702, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-3892003, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-7512222, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-7680959, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-7680960, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-8081736, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-8765711, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-8780508, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-8939696, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-9351806, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-9698569, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-9753693, http://linkedlifedata.com/resource/pubmed/commentcorrection/10548041-9849905
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0961-8368
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1962-70
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Probing the nature of interactions in SH2 binding interfaces--evidence from electrospray ionization mass spectrometry.
pubmed:affiliation
Oxford Centre for Molecular Sciences, New Chemistry Laboratory, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't