Serine protease inhibitor - Definition

Serine protease inhibitors or serpins (short for serine protease inhibitor) are a group of proteins that inhibit peptidases (old name: proteases). Although initially considered a class of protease inhibitors (agents that block the action of protein-degrading enzymes), it was discovered later that it has members that do not inhibit any enzymes, but serve as storage proteins (ovalbumin, in egg white), carriage proteins (thyroxine-binding globulin, steroid-binding globulin) and hormone precursors (angiotensinogen). The term serpin is used for these members as well, despite their noninhibitory function.

Form and function

Serine proteases are defined by the presence of a serine residue in their active domain. The inhibitory serpins have in common that they inhibit this group of enzymes. They 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 sheets and eight or nine alpha helixes in a typical configuration. Mutations in these areas may lead to dysfunction and disease ("serpinopathy").

Specificity

Many serpins are specific for particular proteases (most of them serine proteases), but they can show nonspecific inhibition of other serine proteases as well (e.g. thrombin). Additionally, pathological forms can occasionally inhibit the wrong serine protease.

Members

Proteins in the serpin class:

• Alpha 1-antitrypsin (the most important serpin, often simply referred to as protease inhibitor);
• Alpha 1-antichymotrypsin;
• Alpha 2-antiplasmin (inhibitor of fibrinolysis);
• Antithrombin (inhibitor of coagulation);
• Complement 1-inhibitor;
• Neuroserpin (recently discovered, mutated in some familial forms of );
• Plasminogen activator inhibitor 1 and 2 (fibrinolysis);

Classification

Based on structural similarity, Gettins (2002) classifies the serpins in sixteen clades, with the remaining ten as orphans. He cites evidence that related human serpins may have arisen due to gene duplication, as many are clustered on particular chromosomes.

References

• Gettins PGW. Serpin structure, mechanism and function. Chem Rev 2002;102:4751-803. DOI 10.1021/cr010170+ (http://dx.doi.org/10.1021/cr010170+).

External links

• PDB molecule of the month: Serine protease inhibitor (http://nist.rcsb.org/pdb/molecules/pdb53_1.html)