title: The reaction between plasmin and C1-inhibitor results in plasmin inhibition by the serpin mechanism.
abstract: C1-inhibitor is an important inhibitor of plasma kallikrein and C1, but also has inhibitory activity against numerous other plasma proteinases such as plasmin. The relevance of plasmin inhibition by the C1-inhibitor has been debated, with some evidence showing that plasmin causes significant proteolysis of C1-inhibitor. In the present study, we show that C1-inhibitor in its native state will inhibit plasmin without being significantly degraded, in a manner typical of all serpin reactions. However, if C1-inhibitor is in a denatured polymeric state (as can easily occur during storage, or as produced by heating of the native protein), it will be extensively degraded by plasmin. In addition, we show that hydrophobic interaction chromatography is an effective method to remove trace contaminants of inactive C1-inhibitor polymers.
authors.affiliation: Department of Oral Medicine and Diagnostic Sciences, and Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 60612, USA.
authors.forename: E W
authors.initials: EW
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Ravindran
authors.forename: P A
authors.initials: PA
authors.lastname: Patston
mesh_terms: D001793:Blood Preservation / Q000379:methods*; D002845:Chromatography; D003174:Complement C1 Inactivator Proteins / Q000302:isolation & purification / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein; D015853:Cysteine Proteinase Inhibitors / Q000302:isolation & purification / Q000378:metabolism; D019281:Dimerization; D005341:Fibrinolysin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D011489:Protein Denaturation; D015842:Serine Proteinase Inhibitors; D015843:Serpins
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D015853:Cysteine Proteinase Inhibitors; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D005341:Fibrinolysin