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The role of water molecules in the binding of class I and II peptides to the SH3 domain of the Fyn tyrosine kinase
Author(s) -
Camara-Artigas Ana,
Ortiz-Salmeron Emilia,
Andujar-Sánchez Montserrrat,
Bacarizo Julio,
Martin-Garcia Jose Manuel
Publication year - 2016
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x16012310
Subject(s) - sh3 domain , fyn , tyrosine kinase , proto oncogene tyrosine protein kinase src , chemistry , tyrosine , sh2 domain , receptor tyrosine kinase , binding site , signal transduction , biophysics , biochemistry , biology
Interactions of proline‐rich motifs with SH3 domains are present in signal transduction and other important cell processes. Analysis of structural and thermodynamic data suggest a relevant role of water molecules in these protein–protein interactions. To determine whether or not the SH3 domain of the Fyn tyrosine kinase shows the same behaviour, the crystal structures of its complexes with two high‐affinity synthetic peptides, VSL12 and APP12, which are class I and II peptides, respectively, have been solved. In the class I complexes two water molecules were found at the binding interface that were not present in the class II complexes. The structures suggest a role of these water molecules in facilitating conformational changes in the SH3 domain to allow the binding of the class I or II peptides. In the third binding pocket these changes modify the cation–π and salt‐bridge interactions that determine the affinity of the binding. Comparison of the water molecules involved in the binding of the peptides with previous reported hydration spots suggests a different pattern for the SH3 domains of the Src tyrosine kinase family.