The active site substrate specificity of the cAMP-dependent protein kinase

Phenol Kinase Activity of the Serine/Threonine-Specific cAMP-Dependent Protein Kinase: Steric and Electronic Effects

“…PKA Exhibits a Marked Preference for Phenols Containing Substitutents That Are para to the Alcohol Functional Group. We have previously demonstrated that secondary alcohols serve as poorer PKA substrates than primary alcohols (Kwon et al, 1993a). For example, compound 1 exhibits a 7-fold lower Fmax and a more than 5-fold larger Km than its unsubstituted counterpart 6.…”

l-Dopa: A Powerful Nonphosphorylatable Tyrosine Mimetic for pp60c-src

“…The synthesis of peptides containing unnatural and potentially inhibitory residues can be time-consuming and, in many instances, challenging . Fortunately, these synthetic obstacles can be circumvented by directly attaching the residues of interest to the N- or C-terminus of an active site-directed peptide .…”

“…The synthesis of peptides containing unnatural and potentially inhibitory residues can be time-consuming and, in many instances, challenging . Fortunately, these synthetic obstacles can be circumvented by directly attaching the residues of interest to the N- or C-terminus of an active site-directed peptide . The latter approach provides a rapid and efficient means to acquire peptides containing a structurally diverse ensemble of functionality specifically targeted for active site insertion.…”

“…A dopamine-substituted peptide is not a pp60 c-src substrate. Protein kinases are commonly assayed for activity by quantitating the incorporation of 32 P (from 32 P-γ[ATP]) into serine, threonine, and/or tyrosine residues positioned within positvely charged active site-directed peptides . The latter coordinate to a negatively charged phosphocellulose disk, which can be subsequently counted for radioactivity.…”

Distinguishing between A Mitogenic and Two Closely Related Nonmitogenic Protein Kinases

“…Highly specific inhibitors are not only desirable as probes for elucidating the biochemical consequences of individual protein kinase action but also, as in the case of protein kinase C, may be of significant therapeutic value. Although protein kinases share a common ability to phosphorylate either l -serine/ l -threonine or l -tyrosine amino acids in protein and peptide substrates, we have recently demonstrated that these enzymes will also phosphorylate a structurally diverse ensemble of alcohol-bearing residues not found in eukaryotic proteins . Somewhat surprisingly, the active site preferences of protein kinases can differ, often in a dramatic fashion, toward these unnatural residues.…”