title: Kinetic analysis of ligand-induced autocatalytic reactions.
abstract: Protein phosphorylation and limited proteolysis are two most common regulatory mechanisms involving the energy-dependent covalent modification of regulatory enzymes. In addition to modifying other proteins, many protein kinases and proteases catalyse automodification reactions (i.e. reactions in which the kinase or zymogen serves as its own substrate), and their activities are frequently regulated by other regulatory ligands. In the present study, a kinetic analysis of autocatalytic reaction modulated by regulatory ligands is presented. On the basis of the kinetic equation, a novel procedure is developed to evaluate the kinetic parameters of the reaction. As an example of an application of this method, the effects of calcium ions on the autoacatalytic activation of trypsinogen by trypsin is re-examined. The results indicate that the binding affinity for Ca2+-bound trypsinogen to trypsin is at least two orders of magnitude higher than that for Ca2+-free trypsinogen, and therefore that the effect of Ca2+ ions on K(m*) values for trypsinogen is very much greater than that for the model peptides. Based on the experimental results, one possible molecular mechanism has been proposed.
authors.affiliation: National Laboratory of Biomacromolecules, Center for Molecular Biology, Institute of Biophysics, Academia Sinica, Beijing 100101, People's Republic of China.
authors.forename: Jiang-Hong
authors.initials: JH
authors.lastname: Liu
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002384:Catalysis / Q000187:drug effects; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D013816:Thermodynamics; D014357:Trypsin / Q000378:metabolism*; D014362:Trypsinogen / Q000378:metabolism*
chemical_list: D008024:Ligands; D014362:Trypsinogen; D014357:Trypsin; D002118:Calcium