Protein Name



Homo sapiens (human)

Biological Context

When you cut your skin and break blood vessels in the skin, a complex cascade of various proteins leads to the coagulation of the blood. It produces a kind of natural plug that closes the damaged opening and stops the bleeding. Hemophiliacs, people who are missing some of the proteins in this reaction, are in danger of bleeding to death from even small wounds. On the other hand, blood in the blood vessels may aggregate spontaneously over time. This can lead to ever growing blood clots which in the end close major blood vessels completely, stop the flow of blood to the heart and lead to heart attacks. It is therefore important to be able to understand in detail how blood coagulation happens and to be able to find chemicals by which clotting can be controlled. The coagulation factors in blood are large proteins. One of their domains is a protease, a protein that cuts the peptide bonds in other proteins. Many efforts are being made to find anti-clotting drugs that bind to this protease domain and inhibit its activity. Because proteolytic activity is important to the body harmful side effects may result from such inhibition. It is desirable to find other ways of controlling the proteases. Other potential binding sites, different from the active site, have been found.

Structure Description


The structure here shows an example of such an interaction. The large protein, a dimer of two subunits, is the inhibitory factor. The smaller protein chain is a part of one of the blood coagulation chain proteins, factor X. The two domains of the inhibitory protein form a groove into which the small factor X fragment is embedded. This fragment, in factor X, is responsible for attaching the protein to membranes. When a protein like the inhibitory factor binds to it, it can no longer attach to the membrane and in this way the normal function of factor X is inhibited.

Protein Data Bank (PDB)



Mizuno, H. Fujimoto, Z. Atoda, H. Morita, T.; "Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X."; Proc.Natl.Acad.Sci.USA; (2001) 98:7230-7234 PubMed:11404471.



Author: Arno Paehler

Japanese version:PDB:1IOD