Elastase

In molecular biology, elastase is an enzyme from the class of proteases (peptidases) that break down proteins.

Forms and classification

Eight human genes exist for elastase:

Some bacteria (including Pseudomonas aeruginosa) also produce elastase. In bacteria, elastase is considered a virulence factor.

Function

Elastase breaks down elastin, an elastic fibre that, together with collagen, determines the mechanical properties of connective tissue. The neutrophil form breaks down the Outer membrane protein A (OmpA) of E. coli and other Gram-negative bacteria. Elastase also has the important immunological role of breaking down Shigella virulence factors. This is accomplished through the cleavage of peptide bonds in the target proteins. The specific peptide bonds cleaved are those on the carboxyl side of small, hydrophobic amino acids such as glycine, alanine, and valine. For more on how this is accomplished, see serine protease.

The role of human elastase in disease

A1AT

Elastase is inhibited by the acute-phase protein α₁-antitrypsin (A1AT), which binds almost irreversibly to the active site of elastase and trypsin. A1AT is normally secreted by the liver cells into the serum. α₁-antitryspin deficiency (A1AD) leads to uninhibited destruction of elastic fibre by elastase; the main result is pulmonary emphysema.

Neutrophil elastase

Neutrophil elastase (EC 3.4.21.37, leukocyte elastase, ELANE, ELA2, elastase 2, neutrophil, elaszym, serine elastase) is a serine proteinase in the same family as chymotrypsin and has broad substrate specificity. Secreted by neutrophils and macrophages during inflammation, it destroys bacteria and host tissue. It also localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.

As with other serine proteinases it contains a charge relay system composed of the catalytic triad of histidine, aspartate, and serine residues that are dispersed throughout the primary sequence of the polypeptide but that are brought together in the three dimensional conformation of the folded protein. The gene encoding neutrophil elastase, ELA2, consists of five exons. Neutrophil elastase is closely related to other cytotoxic immune serine proteases, such as the granzymes and cathepsin G. It is more distantly related to the digestive CELA1.

Chymotrypsin-C

Chymotrypsin C, also known as caldecrin or elastase 4 is an enzyme that in humans is encoded by the CTRC gene.

Function

Chymotrypsin C is a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity.

References

Further reading