InterPro domain: IPR000215

Protein protease inhibitors constitute a very important mechanism for regulating proteolytic activity. Serpins (SERine Proteinase INhibitors) belong to MEROPS inhibitor family I4, clan ID. Most serpin family members are indeed serine protease inhibitors, but several have additional cross-class inhibition functions and inhibit cysteine protease family members such as the caspases and cathepsins [ 1 , 2 ]. Others, such as ovalbumin, are incapable of protease inhibition and serve other functions [ 3 ].

The serpins are a functionally diverse family of proteins with a highly conserved structure. Members of the serpin family have been identified in a variety of organisms including animals, viruses, plants [ 4 , 5 ], archaea and bacteria [ 6 , 7 ]. Vertebrate serpins are involved in fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression [ 8 ]. A fungal serpin (celpin) has also been characterised and it is thought to protect the cellulose-degrading apparatus (cellulosome) against proteolytic degradation [ 9 ].

Serpins share a highly conserved core structure that is critical for their functioning as serine protease inhibitors [ 10 , 11 ]. Inhibitory serpins comprise several alpha-helix and beta-strands together with an external reactive centre loop (RCL) containing the active site recognised by the target enzyme. The conserved native fold consists of three beta-sheets (A, B and C) surrounded by alpha-helices (up to nine, A-I) and the RCL. Serpins form covalent complexes with target proteases. Their mechanism of protease inhibition is known as irreversible "trapping" , in which a rapid conformational change traps the cognate protease in a covalent complex resulting in permanent inactivation of both the serpin and its cognate proteinase [ 12 ].

1. Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition. J. Biol. Chem. 269, 19331-7
2. Squamous cell carcinoma antigen is a potent inhibitor of cysteine proteinase cathepsin L. FEBS Lett. 359, 78-80
3. The ovalbumin family of serpin proteins. FEBS Lett. 315, 105-8
4. The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J. Biol. Chem. 276, 33293-6
5. Serpin structure, mechanism, and function. Chem. Rev. 102, 4751-804
6. Serpins in unicellular Eukarya, Archaea, and Bacteria: sequence analysis and evolution. J. Mol. Evol. 59, 437-47
7. Serpins in prokaryotes. Mol. Biol. Evol. 19, 1881-90
8. Serpins: structure, function and molecular evolution. Int. J. Biochem. Cell Biol. 35, 1536-47
9. A serpin in the cellulosome of the anaerobic fungus Piromyces sp. strain E2. Mycol. Res. 112, 999-1006
10. Serpin structure, function and dysfunction. J. Thromb. Haemost. 9 Suppl 1, 26-34
11. Structural and inhibitory effects of hinge loop mutagenesis in serpin-2 from the malaria vector Anopheles gambiae. J Biol Chem 290, 2946-56