The active site substrate specificity of protein kinase C.
The active site substrate specificity of protein kinase C (PKC) has been evaluated. Like the cAMP-dependent protein kinase (PKA), PKC will efficiently phosphorylate archiral residues attached to an active site-directed peptide. In contrast, PKC exhibits behavior that is dramatically different from PKA with respect to the phosphorylation of alpha-substituted alcohols. Although PKA will only phosphorylate residues that contain the same stereochemistry as that found in L-serine, PKC will phosphorylate alpha-configurational isomers that correspond to both the L- and D-stereoisomers. The possible structural basis for the "dual specificity" of PKC is explored. In an analogous vein, although beta-substituted alcohols that serve as PKA substrates must contain the same stereochemistry as that present in L-threonine, PKC will phosphorylate configurational isomers which correspond to both L-threonine and L-allo-threonine. The implications of these observations with respect to protein kinase inhibitor design are discussed.
Kwon
Y G
YG
Department of Chemistry, State University of New York, Buffalo 14214.
Mendelow
M
M
Lawrence
D S
DS
D000438:Alcohols; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
D000438:Alcohols; D009842:Oligopeptides; D010455:Peptides; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C