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PDBsum entry 2o88
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Signaling protein
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PDB id
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2o88
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References listed in PDB file
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Key reference
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Title
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Crystallization by capillary counter-Diffusion and structure determination of the n114a mutant of the sh3 domain of abl tyrosine kinase complexed with a high-Affinity peptide ligand.
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Authors
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A.Cámara-Artigas,
A.Palencia,
J.C.Martínez,
I.Luque,
J.A.Gavira,
J.M.García-Ruiz.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2007,
63,
646-652.
[DOI no: ]
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PubMed id
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Abstract
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The recognition of proline-rich ligands by SH3 domains is part of the process
leading to diseases such as cancer or AIDS. Understanding the molecular
determinants of the binding affinity and specificity of these interactions is
crucial for the development of potent inhibitors with therapeutic potential. In
this study, the crystallographic structure of the N114A mutant of the SH3 domain
of the Abelson leukaemia virus tyrosine kinase complexed with a high-affinity
peptide is presented. The crystallization was carried out using the capillary
counter-diffusion technique, which facilitates the screening, manipulation and
transport of the crystals and allows the collection of X-ray data directly from
the capillary in which the crystals were grown. The crystals of the N114A mutant
belong to the orthorhombic P2(1)2(1)2(1) space group, with unit-cell parameters
a = 48.2, b = 50.1, c = 56.4 A. The quality of the diffraction data set has
allowed the structure of the complex to be determined at a resolution limit of
1.75 A.
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Figure 2.
Figure 2 Overall fold of the N114A mutant of the SH3 domain of
Ab1 in complex with the p41 decapeptide. Residues in the SH3
domain-binding site are shown as green sticks. The decapeptide
p41 is shown as yellow sticks. The proline residues interacting
with the three hydrophobic pockets (pocket 1, Tyr70/Tyr115;
pocket 2, Tyr115/Phe72/Trp99; pocket 3, Trp99/Trp110/Asn78) in
the SH3 domain are indicated.
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Figure 5.
Figure 5 Superposition of the N114 Abl-SH3-p41 complex (cyan)
and the Abl tyrosine kinase structure (PDB code 1opk ; pale
green). The SH2-kinase linker implicated in regulation of the
kinase activity is coloured orange. Relevant water molecules are
shown as red spheres.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2007,
63,
646-652)
copyright 2007.
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