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PDBsum entry 3eg3
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References listed in PDB file
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Key reference
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Title
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Role of interfacial water molecules in proline-Rich ligand recognition by the src homology 3 domain of abl.
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Authors
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A.Palencia,
A.Camara-Artigas,
M.T.Pisabarro,
J.C.Martinez,
I.Luque.
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Ref.
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J Biol Chem, 2010,
285,
2823-2833.
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PubMed id
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Abstract
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The interaction of Abl-Src homology 3 domain (SH3) with the high affinity
peptide p41 is the most notable example of the inconsistency existing between
the currently accepted description of SH3 complexes and their binding
thermodynamic signature. We had previously hypothesized that the presence of
interfacial water molecules is partially responsible for this thermodynamic
behavior. We present here a thermodynamic, structural, and molecular dynamics
simulation study of the interaction of p41 with Abl-SH3 and a set of mutants
designed to alter the water-mediated interaction network. Our results provide a
detailed description of the dynamic properties of the interfacial water
molecules and a molecular interpretation of the thermodynamic effects elicited
by the mutations in terms of the modulation of the water-mediated hydrogen bond
network. In the light of these results, a new dual binding mechanism is proposed
that provides a better description of proline-rich ligand recognition by Abl-SH3
and that has important implications for rational design.
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Secondary reference #1
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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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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
reproduced from the cited reference
with permission from the IUCr
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