Structural Medicine Serpins

The Serpin Database
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Serpins

Antithrombin with bound pentasaccharide.
Click on the picture for VRML tour of serpin structure

The serpins is an acronymic name given to a family of serine protease inhibitors that share a complex, but well conserved, tertiary structure. Members of the family are diversely present in eukaryotes, plants and viruses, and are evident in everyday life from the white of the breakfast egg - the non-inhibitory serpin ovalbumin, to the foam protein of the evening beer - the barley Z protease inhibitor.

Notably, the serpins are the principle protease inhibitors in human plasma :

antithrombin controls the proteolytic coagulation cascade;
C1-inhibitor controls complement activation;
the plasminogen activator inhibitors, PAI-1 and PAI-2, control fibrinolysis;
and alpha-1-antitrypsin, also called alpha-1-proteinase inhibitor, modulates connective tissue restructuring.

Altogether the inhibitory serpins make up some 10% in molar terms, of the proteins in human plasma. Also present, in plasma, though in smaller concentrations, are other serpins that have lost their inhibitory activity but have taken on other functions vital to life; examples are the vasopressor peptide source angiotensinogen, and the thyroxine and corticosteroid binding globulins, TBG and CBG.

The reason for the evolutionary success of the serpins is their possession, uniquely amongst the many families of serine protease inhibitors, of a mobile reactive site loop. It is the ability of this loop to profoundly change its conformation that enables the serpins to bind to their target proteases as a virtually irreversible complex.