title: Temperature dependence of the thrombin-catalyzed proteolysis of prothrombin.
abstract: Measurement of the temperature-dependence of thrombin-catalyzed cleavage of the Arg(155)-Ser(156) and Arg(284)-Thr(285) peptide bonds in prothrombin and prothrombin-derived substrates has yielded Arrhenius parameters that are far too large for classical mechanistic interpretation in terms of a simple hydrolytic reaction. Such a difference from the kinetic behavior exhibited in trypsin- and chymotrypsin-catalyzed proteolysis of peptide bonds is attributed to contributions by enzyme exosite interactions as well as enzyme conformational equilibria to the magnitudes of the experimentally determined Arrhenius parameters. Although the pre-exponential factor and the energy of activation deduced from the temperature-dependence of rate constants for proteolysis by thrombin cannot be accorded the usual mechanistic significance, their evaluation serves a valuable role by highlighting the existence of contributions other than those emanating from simple peptide hydrolysis to the kinetics of proteolysis by thrombin and presumably other enzymes of the blood coagulation system.
authors.affiliation: American Red Cross Blood Services, Detroit, MI 48232, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Shi
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Winzor
authors.forename: Craig M
authors.initials: CM
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology; D002384:Catalysis; D002918:Chymotrypsin / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011516:Prothrombin / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D013912:Threonine; D012694:Serine; D011516:Prothrombin; D001120:Arginine; D002918:Chymotrypsin; D014357:Trypsin; D013917:Thrombin