The role of water molecules in the binding of class I and II peptides to the SH3 domain of the Fyn tyrosine kinase.
Acta Crystallogr F Struct Biol Commun
; 72(Pt 9): 707-12, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27599862
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Água
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Proteínas Proto-Oncogênicas c-fyn
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article