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Chemistry and Biology of Serpins pp 185–194Cite as

C1 Inhibitor

Functional Analysis of Naturally-Occurring Mutant Proteins

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 425))

Abstract

C1 inhibitor, although frequently considered primarily a complement protein, is able to inactivate proteinases that participate in several different proteolytic cascades, and is essential in the regulation of activation of both the complement system and the contact system of kinin formation. It also may serve a backup function in regulation of coagulation and of fibrinolysis. C1 inhibitor, therefore, is most important in host defense and in the mediation of vascular permeability. Its name is derived from its discovery as the inactivator of the first complement component. This came about as a result of the studies of Lepow and his colleagues in the late 1950s and early 1960s; these were directed toward the isolation of C1 and its constituent subunits: C1q, C1r and C1s1–5. C1 inhibitor was characterized as a heat labile serum protein that inhibited the esterolytic activity of C1 and its proteolytic activity against C4 and C2. It subsequently was shown to inactivate several other plasma proteases, including kallikrein, plasmin, tissue plasminogen activator, and coagulation factors XIa and XIIa (Hageman factor)5–10. The fact that C1 inhibitor inactivated proteases by formation of denaturant stable equimolar complexes was first clearly shown by Harpel and Cooper with both C1s and plasmin6. Cl inhibitor does not appear to differ in any significant way from other serpins in its mechanism of action. The P1 and P1’ residues are arginine and threonine, respectively11.

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Author information

Authors and Affiliations

  1. Division of Nephrology, Children’s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio, 45229-3039, USA

    Alvin E. Davis III

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  1. Alvin E. Davis III
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Editor information

Editors and Affiliations

  1. University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

    Frank C. Church

  2. University of California, Irvine, California, USA

    Dennis D. Cunningham

  3. Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan, USA

    David Ginsburg

  4. Duke University and Durham VA Medical Centers, Durham, North Carolina, USA

    Maureane Hoffman

  5. Late of Monash University, Clayton, Victoria, Australia

    Stuart R. Stone

  6. Washington University School of Medicine, St. Louis, Missouri, USA

    Douglas M. Tollefsen

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Davis, A.E. (1997). C1 Inhibitor. In: Church, F.C., Cunningham, D.D., Ginsburg, D., Hoffman, M., Stone, S.R., Tollefsen, D.M. (eds) Chemistry and Biology of Serpins. Advances in Experimental Medicine and Biology, vol 425. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5391-5_18

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  • DOI: https://doi.org/10.1007/978-1-4615-5391-5_18

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