1bu1
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(New page: 200px<br /> <applet load="1bu1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bu1, resolution 2.6Å" /> '''SRC FAMILY KINASE HC...)
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Revision as of 11:48, 8 November 2007
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SRC FAMILY KINASE HCK SH3 DOMAIN
Overview
Understanding the issue of specificity imposed in the interactions of SH3, domains has largely been addressed in studies investigating the, interaction of proline-rich amino acid sequences derived from potential, ligands for these domains. Although the interaction with this motif forms, an essential platform in the binding of SH3 domains, in many cases little, specificity is observed and the difference in affinity for so-called, specific and nonspecific proline-rich sequences is not great. Furthermore, the binding interface between an SH3 domain and a protein ligand appears, to encompass more interactions than are represented by that involving the, proline-rich motif. Here we investigate the issue of specificity from the, opposite point of view; namely, how does a ligand recognize different SH3, domains? We present the crystal structure of the unbound SH3 domain from, hemopoietic cell kinase (Hck) which is a member of the Src family of, tyrosine kinases. This structure reveals that, unlike the structures of, other Src kinase SH3 domains, the RT loop region is highly mobile and, lacks a network of hydrogen bonds that is elsewhere apparent. The RT loop, has been shown to form a major part of the binding interface between SH3, domains and HIV-1 Nef. Thermodynamic data, derived from isothermal, titration calorimetry, for the binding of Hck SH3 to HIV-1 Nef show that, the binding of Hck (KD = 1.5 microM) is approximately an order of, magnitude tighter than those of other Src family kinases that were, investigated (Fyn, Lck, and Src). This increase in affinity is attributed, to, among other effects, the inherent flexibility in the RT loop which, does not require breaking the network of hydrogen bonds to adopt the, conformation required for binding.
About this Structure
1BU1 is a Single protein structure of sequence from Homo sapiens. 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.
Reference
RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef., Arold S, O'Brien R, Franken P, Strub MP, Hoh F, Dumas C, Ladbury JE, Biochemistry. 1998 Oct 20;37(42):14683-91. PMID:9778343
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