The active site substrate specificity of the cAMP-dependent protein kinase.
cAMP-dependent protein kinase substrates have been synthesized employing an unusually efficient method that allows the alcohol-bearing residue to be incorporated into the peptide after solid phase peptide synthesis. These peptide substrates have been utilized to map the active site substrate specificity of the protein kinase. Only alpha- or beta-substituted alcohol-bearing residues containing the proper absolute configuration are phosphorylated by the enzyme. However, the cAMP-dependent protein kinase will phosphorylate achiral residues. The implications of the observed protein kinase substrate specificity with respect to inhibitor design are discussed.
Department of Chemistry, State University of New York, Buffalo 14214.
Y G
YG
Kwon
M
M
Mendelow
J
J
Srinivasan
T R
TR
Lee
S
S
Pluskey
A
A
Salerno
D S
DS
Lawrence
D000438:Alcohols; D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000438:Alcohols; D009842:Oligopeptides; D011494:Protein Kinases