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Quantitative Structure–Activity Relationships in the Protein Kinase C Reaction with Synthetic Peptides Derived from Myelin Basic Protein

✍ Scribed by Jaak Järv; Katrin Sak; Marika Eller; Pia Ek; Åke Engström; Lorentz Engström


Publisher
Elsevier Science
Year
1996
Tongue
English
Weight
145 KB
Volume
24
Category
Article
ISSN
0045-2068

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✦ Synopsis


and His, was synthesized and the kinetics of their phosphorylation by protein kinase C was studied. All compounds, except the peptide with Pro at the position X, were effectively phosphorylated by this enzyme, and for these substrates the kinetic constants K m , maximal velocity constants V, and second-order rate constants k II were determined. The data were analyzed by means of quantitative structure-activity relationships, taking into account hydrophobicity of the variable amino acids, bulkiness of their side groups quantified by molecular refractivity constants MR, and ionic status of these substituents by using an independent variable ϩ1 for cationic, Ϫ1 for anionic, and 0 for nonionic substituents. These structural factors influenced the K m values, while the maximal velocity of phosphorylation depended mostly on the ionic status of the variable amino acid. The latter effect seems to characterize electrostatic interaction between the substrate molecule and some negative charge located in the enzyme active center.