%0 Journal Article
%T Allosteric Cooperativity in Inhibition of Protein Kinase a Catalytic Subunit
%A Aleksei KuznetsovJaak J rvS
%J The Open Enzyme Inhibition Journal
%D 2008
%I 
%R 10.2174/1874940200801010042]
%X Allosteric cooperativity in inhibition of protein kinase A was studied for the first time kinetically, by using the second-order rate constants of kemptide phosphorylation, measured in the absence and presence of inhibitors, and the effect of cooperativity was characterized in terms of the interaction factor ¦Ã. This kinetic method was evaluated for differently targeted inhibitors H89 and LRRAALG-NH2, and interaction of these compounds with the free enzyme and the enzyme- substrate complexes was quantified. The inhibitory effect of these compounds was asymmetric relatively ATP and kemptide, and allosteric enhancement of LRRAALG-NH2 binding in the presence of ATP was revealed. This cooperative effect was compared with results of ligand binding studies and the principle  better binding - stronger allostery  was formulated and formalized in terms of a linear-free-energy relationship p(¦Ã) = C + S pKi, where p(¦Ã) stands for the negative logarithm of the interaction factor and pKi characterizes affinity of the free enzyme for the inhibitory peptide, C=-2.7 and S=0.9, r=0.92.
%U http://www.benthamscience.com/open/toeij/articles/V001/42TOEIJ.htm