Plasma kallikrein

Function

Plasma prekallikrein is a glycoprotein that participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. It is synthesized in the liver and secreted into the blood as a single polypeptide chain. Plasma prekallikrein is converted to plasma kallikrein by factor XIIa by the cleavage of an internal Arg-Ile bond. Plasma kallikrein therefore is composed of a heavy chain and a light chain held together by a disulfide bond. The heavy chain originates from the amino-terminal end of the zymogen and contains 4 tandem repeats of 90 or 91 amino acids. Each repeat harbors a novel structure called the apple domain. The heavy chain is required for the surface-dependent pro-coagulant activity of plasma kallikrein. The light chain contains the active site or catalytic domain of the enzyme and is homologous to the trypsin family of serine proteases. Plasma prekallikrein deficiency causes a prolonged activated partial thromboplastin time in patients.

Interactions

Kallikrein and prekallikrein have been shown to interact with High-molecular-weight kininogen.

References

References

1. (1981). "Bovine and human plasma prekallikrein".
2. (December 1981). "Mapping the active sites of bovine thrombin, factor IXa, factor Xa, factor XIa, factor XIIa, plasma kallikrein, and trypsin with amino acid and peptide thioesters: development of new sensitive substrates". Biochemistry.
3. (1988). "Prekallikrein".
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5. (November 1989). "Synthesis of tripeptide chloromethyl ketones and examination of their inhibitory effects on plasmin and plasma kallikrein". Chemical & Pharmaceutical Bulletin.
6. (April 1998). "Identification of human plasma kallikrein gene polymorphisms and evaluation of their role in end-stage renal disease". Hypertension.
7. (August 1986). "Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats". Biochemistry.
8. "Entrez Gene: KLKB1 kallikrein B, plasma (Fletcher factor) 1".
9. (October 1979). "Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain". Proc. Natl. Acad. Sci. U.S.A..
10. (October 1994). "Localization of the binding site on plasma kallikrein for high-molecular-weight kininogen to both apple 1 and apple 4 domains of the heavy chain". Arch. Biochem. Biophys..
11. (July 1993). "Mapping of the high molecular weight kininogen binding site of prekallikrein. Evidence for a discontinuous epitope formed by distinct segments of the prekallikrein heavy chain". J. Biol. Chem..
12. (September 1999). "Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2". J. Biol. Chem..