Information About

Serine Protease Inhibitor





FORM AND FUNCTION

Serine Protease s are defined by the presence of a Serine residue in their active domain (e.g. Thrombin ). Most inhibitory ''serpins'' inhibit this group of Enzyme s. Some serpins, particularly the squamous cell carcinoma antigen 1 ( SCCA1 ), have been shown to inhibit Cysteine Protease s using the same mechanism as other serpins use to inhibit serine proteases. Cysteine proteases differ from serine proteases in that they are defined by the presence of a Cysteine residue, rather than a serine residue, in their active domain. Nonetheless, the enymatic chemistry is similar, which is one possible reason why serpins can inhibit them. Serpins are part of the larger group of Protease Inhibitors .

Although the function of serpins varies widely, they share a number of structural details: all have three Beta Sheet s and eight or nine Alpha Helix es in a typical configuration. Serpins also posess an exposed region, called the reactive centre (or site) loop that determines which proteases are targeted for inhibition. Many Mutation s have been described that lead to serpin dysfunction and diseases ("serpinopathies") such as emphysema, thrombosis and dementia.


SPECIFICITY

Most serpins are specific for a particular protease (usually a serine protease), but in the laboratory many can show inhibition of several other proteases as well. Additionally, pathological forms can occasionally inhibit the ''wrong'' serine protease. The physiological target of a serpin will be dictated not only by the ability to inhibit a given protease, but in what place and at what time that protease is found. For example antitrypsin is able to inhibit trypsin (a digestive enzyme), but its primary physiological target is elastase (in the lungs). This is something that scientists must take into account when they identify a new serpin-enzyme interaction in the laboratory.


EVOLUTION

Serpins were initially believed to be restricted to Eukaryote organisms, but have since been found in a number of Bacteria and Archaea (Irving ''et al''). It remains unclear whether these prokaryote genes are the descendants of an ancestral prokaryotic serpin or whether they are the product of lateral gene transfer (genetic transfer between organsisms not by evolutionary descent).


MEMBERS

Proteins in the ''serpin'' class:


CLASSIFICATION

In 2001 , a consensus (Silverman ''et al'') was published in which the circa 500 serpins were classified in sixteen Clade s (based on structural similarity), with the remaining ten as orphans. Gettins (2002) cites evidence that related human serpins may have arisen due to recent Gene Duplication , as many form discrete clusters on particular Chromosome s.


REFERENCES

  • Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, Gettins PG, Irving JA, Lomas DA, Luke CJ, Moyer RW, Pemberton PA, Remold-O'Donnell E, Salvesen GS, Travis J, Whisstock JC. ''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 2001;276:33293-6. PMID 11435447.

  • Gettins PGW. ''Serpin structure, mechanism and function''. Chem Rev 2002;102:4751-803. DOI 10.1021/cr010170+ .

  • Irving JA, Steenbakkers PJ, Lesk AM, Op den Camp HJ, Pike RN, Whisstock JC. ''Serpins in prokaryotes.'' Mol Biol Evol. 2002 Nov;19(11):1881-90. PMID: 12411597.

  • Irving JA, Pike RN, Lesk AM, Whisstock. ''Phylogeny of the Serpin Superfamily: Implications of Patterns of Amino Acid Conservation for Structure and Function.'' Genome Res. 2006; 10; 1845-64.



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