Increasing the kinase specificity of k252a by protein surface recognition |
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Authors: | Schneider Tanya L Mathew Rebecca S Rice Kevin P Tamaki Kazuhiko Wood John L Schepartz Alanna |
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Affiliation: | Department of Chemistry and Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8107, USA. |
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Abstract: | [reaction: see text] Here we describe a miniature protein (1) that presents the cAMP-dependent protein kinase (PKA) recognition epitope found within the heat-stable Protein Kinase Inhibitor protein (PKI) and a miniature protein conjugate (1-K252a) in which 1 is joined covalently to the high-affinity but nonselective kinase inhibitor K252a. Miniature protein 1 recognizes PKA with an affinity that rivals that of PKI and, in the context of 1-K252a, leads to a dramatic increase in kinase specificity. |
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