Kinetics and thermodynamics of the slow hydrophobic deactivation of alpha-chymotrypsin.
A quantitative model for the slow reversible hydrophobic deactivation of alpha-chymotrypsin (alpha-CT) is proposed. Kinetic results are obtained for (1) the situation in which the inhibitor concentration, although remaining constant during the course of a run, can be varied independently of the concentration of nonself-inhibiting substrate, and for (2) the situation in which the self-inhibiting substrate concentration decreases during the course of a run, and independent variation of inhibitor and substrate concentrations is not possible. Excellent quantitative agreement between theory and experiment is obtained for a wide range of conditions using 3-(n-hexanoyl-O-benzoate (with dodecylsulfate as the inhibitor), and 3-(n-decanoyl)-O-benzoate as the self-inhibiting substrate. Activation enthalpies and entropies for the hydrophobic deactivation of alpha-CT by dodecylsulfate and tetradecyltrimethylammonium are determined. For comparison, activation enthalpies and entropies for the alpha-CT hydrolysis of 3-(n-heptanoyl)-O-benzoate are determined; evidence for a thermally induced conformational transition in alpha-CT at 30 degrees C is obtained.
D001565:Benzoates; D001665:Binding Sites; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D007700:Kinetics; D008433:Mathematics; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D001565:Benzoates; D002918:Chymotrypsin