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. 1968 Oct 1;128(4):571–593. doi: 10.1084/jem.128.4.571

THE ENZYMATIC NATURE OF C'1r

CONVERSION OF C'1s TO C'1 ESTERASE AND DIGESTION OF AMINO ACID ESTERS BY C'1r

George B Naff 1, Oscar D Ratnoff 1
PMCID: PMC2138543  PMID: 5675434

Abstract

Human C'1, a macromolecular complex composed of three subunits, is the zymogen for at least two distinct enzymes. Preparations of one subunit, C'1r, functioned as a protease which converted another subunit, C'1s, to C'1 esterase. The conversion of C'1s to C'1 esterase by C'1r was blocked by Liquoid, phenyl methylsulfonyl fluoride, and calcium ions, but not by soybean trypsin inhibitor, hirudin, or heparin. Preparations of C'1r also possessed two additional functions, i.e., the ability to hydrolyze certain synthetic amino acid esters and to participate in immune hemolysis. Evidence was presented which indicates that these three functions are properties of a single entity, C'1r, but not of the same portion of its molecular structure. These observations suggest that C'1r has at least two active sites, one for its reaction with C'1q, an additional subunit of C'1, and one for its reaction with C'1s; together, the three subcomponents, C'1q, C'1r, and C'1s, form a single functional unit, the first component of complement.

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Selected References

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  1. BECKER E. L. Concerning the mechanism of complement action. II. The nature of the first component of guinea pig complement. J Immunol. 1956 Dec;77(6):469–478. [PubMed] [Google Scholar]
  2. ERLANGER B. F., KOKOWSKY N., COHEN W. The preparation and properties of two new chromogenic substrates of trypsin. Arch Biochem Biophys. 1961 Nov;95:271–278. doi: 10.1016/0003-9861(61)90145-x. [DOI] [PubMed] [Google Scholar]
  3. Freisheim J. H., Walsh K. A., Neurath H. The activation of bovine procarboxypeptidase A. II. Mechanism of activation of the succinylated enzyme precursor. Biochemistry. 1967 Oct;6(10):3020–3028. doi: 10.1021/bi00862a008. [DOI] [PubMed] [Google Scholar]
  4. HAINES A. L., LEPOW I. H. STUDIES ON HUMAN C'1-ESTERASE. I. PURIFICATION AND ENZYMATIC PROPERTIES. J Immunol. 1964 Mar;92:456–467. [PubMed] [Google Scholar]
  5. KENT J. F., OTERO A. G., HARRIGAN R. E. Relative specificity of serologic tests for syphilis in Mycobacterium leprae infection. Am J Clin Pathol. 1957 May;27(5):539–545. doi: 10.1093/ajcp/27.5.539. [DOI] [PubMed] [Google Scholar]
  6. KLEIN P., LANGE A. Uber die Reaktivierung von Komplement nach Vergiftung durch hochmolekulare Anticoagulantien. Z Hyg Infektionskr. 1956;142(5):445–456. [PubMed] [Google Scholar]
  7. KLEIN P. Untersuchungen über den Angriffspunkt von gerinnungshemmenden Stoffen am Komplement. Z Hyg Infektionskr. 1956;142(5):457–475. [PubMed] [Google Scholar]
  8. KLINE D. L., FISHMAN J. B. Proactivator function of human plasmin as shown by lysine esterase assay. J Biol Chem. 1961 Oct;236:2807–2812. [PubMed] [Google Scholar]
  9. LEPOW I. H., NAFF G. B., TODD E. W., PENSKY J., HINZ C. F. Chromatographic resolution of the first component of human complement into three activities. J Exp Med. 1963 Jun 1;117:983–1008. doi: 10.1084/jem.117.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LEPOW I. H., RATNOFF O. D., PILLEMER L. Elution of an esterase from antigen-antibody aggregates treated with human complement. Proc Soc Exp Biol Med. 1956 May;92(1):111–114. doi: 10.3181/00379727-92-22401. [DOI] [PubMed] [Google Scholar]
  11. NAFF G. B., PENSKY J., LEPOW I. H. THE MACROMOLECULAR NATURE OF THE FIRST COMPONENT OF HUMAN COMPLEMENT. J Exp Med. 1964 Apr 1;119:593–613. doi: 10.1084/jem.119.4.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Prentice C. R., Ratnoff O. D., Breckenridge R. T. Experiments on the nature of the prothrombin-converting principle: alteration of proaccelerin by thrombin. Br J Haematol. 1967 Nov;13(6):898–914. doi: 10.1111/j.1365-2141.1967.tb08860.x. [DOI] [PubMed] [Google Scholar]
  13. RASMUSSEN P. S. Purification of thrombin by chromatography. Biochim Biophys Acta. 1955 Jan;16(1):157–158. doi: 10.1016/0006-3002(55)90194-3. [DOI] [PubMed] [Google Scholar]
  14. RATNOFF O. D., LEPOW I. H. Some properties of an esterase derived from preparations of the first component of complement. J Exp Med. 1957 Aug 1;106(2):327–343. doi: 10.1084/jem.106.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ratnoff O. D. INCREASED VASCULAR PERMEABILITY INDUCED BY HUMAN PLASMIN. J Exp Med. 1965 Oct 31;122(5):905–921. doi: 10.1084/jem.122.5.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ratnoff O. D., Naff G. B. The conversion of C'IS to C'1 esterase by plasmin and trypsin. J Exp Med. 1967 Feb 1;125(2):337–358. doi: 10.1084/jem.125.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. SIEGELMAN A. M., CARLSON A. S., ROBERTSON T. Investigation of serum trypsin and related substances. I. The quantitative demonstration of trypsinlike activity in human blood serum by a micromethod. Arch Biochem Biophys. 1962 Apr;97:159–163. doi: 10.1016/0003-9861(62)90058-9. [DOI] [PubMed] [Google Scholar]
  18. Sherry S., Alkjaersig N., Fletcher A. P. Comparative activity of thrombin on substituted arginine and lysine esters. Am J Physiol. 1965 Sep;209(3):577–583. doi: 10.1152/ajplegacy.1965.209.3.577. [DOI] [PubMed] [Google Scholar]

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