2eu0
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The NMR ensemble structure of the Itk SH2 domain bound to a phosphopeptide
OverviewOverview
The Src homology 2 (SH2) domain of interleukin-2 tyrosine kinase (Itk) is, a critical component of the regulatory apparatus controlling the activity, of this immunologically important enzyme. To gain insight into the, structural features associated with the activated form of Itk, we have, solved the NMR structure of the SH2 domain bound to a, phosphotyrosine-containing peptide (pY) and analyzed changes in, trans-hydrogen bond scalar couplings ((3h)J(NC')) that result from pY, binding. Isomerization of a single prolyl imide bond in this domain is, responsible for simultaneous existence of two distinct SH2 conformers., Prolyl isomerization directs ligand recognition: the trans conformer, preferentially binds pY. The structure of the SH2/pY complex provides, insight into the ligand specificity; the BG loop in the ligand-free trans, SH2 conformer is pre-arranged for optimal contacts with the pY+3 residue, of the ligand. Analysis of (3h)J(NC') couplings arising from hydrogen, bonds has revealed propagation of structural changes from the pY binding, pocket to the CD loop containing conformationally heterogeneous proline as, well as to the alphaB helix, on the opposite site of the domain. These, findings offer a structural framework for understanding the roles of, prolyl isomerization and pY binding in Itk regulation.
About this StructureAbout this Structure
2EU0 is a Protein complex structure of sequences from Mus musculus with ACE and NH2 as ligands. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
ReferenceReference
Molecular details of Itk activation by prolyl isomerization and phospholigand binding: the NMR structure of the Itk SH2 domain bound to a phosphopeptide., Pletneva EV, Sundd M, Fulton DB, Andreotti AH, J Mol Biol. 2006 Mar 24;357(2):550-61. Epub 2006 Jan 18. PMID:16436281
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