Application of linear free energy relationships to the serpin-proteinase inhibition mechanism.
Linear free energy relationships can be used to link the changes in rate constant for a reaction to changes in the equilibrium caused by alterations in structure. While they have most often been used in the analysis of chemical reactions, they have also been employed to resolve questions in enzymology and protein folding. Here we analyze the reaction of a serpin with a panel of six serine proteinases, and observe that a linear free energy relationship exists between the true second-order rate constant for reaction, k(inh), and the inhibition constant, K(I), indicating that formation of the covalent serpin-enzyme complex may be reversible.
Nash
P
P
Department of Biochemistry, University of Alberta, Edmonton, Canada.
McFadden
G
G
Whitty
A
A
D000818:Animals; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D007700:Kinetics; D017510:Protein Folding; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D015843:Serpins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D015842:Serine Proteinase Inhibitors; D015843:Serpins; D010450:Endopeptidases