serine protease

Wikipedia

Definition: Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.

Serine proteases are found ubiquitously in both eukaryotes and prokaryotes.

Serine proteases fall into two broad categories based on their structure:
 chymotrypsin-like (trypsin-like)
 subtilisin-like.

In humans, they are responsible for co-ordinating various physiological functions, including digestion, immune response, blood coagulation and reproduction.

Chymotrypsin-like (trypsin-like)

Chymotrypsin-like serine proteases are characterised by a distinctive structure, consisting of two beta-barrel domains that converge at the catalytic active site. These enzymes can be further categorised based on their substrate specificity as either trypsin-like, chymotrypsin-like or elastase-like.

Trypsin-like proteases cleave peptide bonds following a positively charged amino acid (lysine or arginine). This specificity is driven by the residue which lies at the base of the enzyme’s S1 pocket (generally a negatively charged aspartic acid or glutamic acid).

Chymotrypsin-like

The S1 pocket of chymotrypsin-like enzymes is more hydrophobic than in trypsin-like proteases. This results in a specificity for medium to large sized hydrophobic residues, such as tyrosine, phenylalanine and leucine.

Elastase-like

Elastase-like proteases have a much smaller S1 cleft than either trypsin- or chymotrypsin-like proteases. Consequently, residues such as alanine, glycine and valine tend to be preferred.

Subtilisin-like

Subtilisin is a serine protease in prokaryotes. Subtilisin is evolutionary unrelated to the chymotrypsin-clan, but shares the same catalytic mechanism utilising a catalytic triad, to create a nucleophilic serine.

This is the classic example used to illustrate convergent evolution, since the same mechanism evolved twice independently during evolution.

Pathology

Mutations may lead to decreased or increased activity of enzymes. This may have different consequences, depending on the normal function of the serine protease.

For example, mutations in protein C, when leading to insufficient protein levels or activity, predispose to thrombosis.

Diagnostic use

Determination of serine protease levels may be useful in the context of particular diseases.

 coagulation factor levels may be required in the diagnosis of hemorrhagic or thrombotic conditions.
 fecal elastase is employed to determine the exocrine activity of the pancreas, e.g., in cystic fibrosis or chronic pancreatitis.
 serum prostate-specific antigen is used in prostate cancer screening, risk stratification, and post-treatment monitoring.

See also

  pathology of serpins (serpinopathies)

• SPINK5 deficiency (Netherton disease)