Phenothiazine-N-carbonyl chloride, a specific inactivator of chymotrypsin.
Phenothiazine-N-carbonyl chloride inactivated chymotrypsin and trypsin by means of a 1:1 stoicheiometric reaction. Its reaction with chymotrypsin was 29 times as fast as that with trypsin and was inhibited by indole. The reaction of phenothiazine-N-carbonyl chloride with chymotrypsin resembled an enzyme-substrate reaction in which the deacylation step is rate-limiting. Slow deacylation occurred, resulting in complete regeneration of active enzyme in 15h. The pH-rate profile of the inactivation process had a maximum at pH7.8. These data and other evidence indicate that the reaction of phenothiazine-N-carbonyl chloride with chymotrypsin exhibits ;kinetic specificity'. Therefore any hypothesis that attempts to describe the topography of the active site of chymotrypsin should take into account the reactivity of phenothiazine-N-carbonyl chloride. The above findings, as well as recent reports of others, are examined within the context of a hypothesis given in an earlier paper (Erlanger, 1967).
D001665:Binding Sites; D002712:Chlorides; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D010640:Phenothiazines / Q000494:pharmacology*; D014361:Trypsin Inhibitors
D002712:Chlorides; D007211:Indoles; D010640:Phenothiazines; D014361:Trypsin Inhibitors; D002918:Chymotrypsin