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Semisynthetic Src SH2 domains demonstrate altered phosphopeptide specificity induced by incorporation of unnatural lysine derivatives

Virdee, S. and Macmillan, D. and Waksman, Gabriel (2010) Semisynthetic Src SH2 domains demonstrate altered phosphopeptide specificity induced by incorporation of unnatural lysine derivatives. Chemistry & Biology 17 (3), pp. 274-284. ISSN 1879-1301.

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Official URL: http://dx.doi.org/10.1016/j.chembiol.2010.01.015

Abstract

Site-directed mutagenesis to the 20 natural amino acids becomes a limitation when evaluating subtle perturbations of an amino acid side chain within a protein. To further the study of Src homology 2 (SH2) domain ligand binding, we have developed a system allowing its semisynthesis from three fragments by native chemical ligation. We have replaced a key lysine residue with lysyl derivatives possessing progressively shorter aliphatic side chains. Biophysical characterization of these SH2 domain analogs has allowed for the first time a systematic dissection of the side chain length contribution from a lysine residue to ligand binding. We show that the specificity of the SH2 domain of the Src kinase can be altered by incorporation of such lysyl derivatives, thereby demonstrating the potential of the technique for the development of SH2 domain-based research tools and therapeutics.

Item Type: Article
Keyword(s) / Subject(s): Chembio, signaling, cellbio
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 04 Aug 2010 14:09
Last Modified: 17 Apr 2013 12:17
URI: http://eprints.bbk.ac.uk/id/eprint/1178

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