In molecular biology, elastase is an enzyme from the class of (peptidases) that break down ,
Forms and classification
Eight human
exist for elastase:
|
|
|
chymotrypsin-
like | CELA1 | ELA1 | chymotrypsin-like elastase family, member 1 | elastase 1, pancreatic | |
| CELA2A | ELA2A | chymotrypsin-like elastase family, member 2A | elastase 2A, pancreatic | |
| CELA2B | ELA2B | chymotrypsin-like elastase family, member 2B | elastase 2B, pancreatic | |
| CELA3A | ELA3A | chymotrypsin-like elastase family, member 3A | elastase 3A, pancreatic | |
| CELA3B | ELA3B | chymotrypsin-like elastase family, member 3B | elastase 3B, pancreatic | |
| chymotrypsin | Chymotrypsin-C | ELA4 | chymotrypsin C (caldecrin) | elastase 4 | |
| neutrophil | ELANE | ELA2 | neutrophil elastase | elastase 2 | |
| macrophage | MMP12 | HME | macrophage metalloelastase | macrophage elastase | |
The four "pancreatic elastases", chymotrypsin, and neutrophil elastase are .
Chymotrypsin is weaker at digesting elastin than the archetypical pancreatic elastase.
Some bacteria (including Pseudomonas aeruginosa) also produce elastase; bacterial elastases work in many ways and include , aspartic proteases, , and .
Function
The fact that elastase can break down
elastin in test tubes (while other proteases cannot) does not imply that there is a unifying function for all elastases in the living body. Instead, they each have their own role:
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The pancreatic elastase (as well as chymotrypsin) is responsible for digesting proteins in food. Note that "pancreatic elastase 1" is, in fact, not found in the pancreas, but produced in the skin.
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"Pancreatic elastase 1" (CELA1) is expressed in skin .
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Neutrophil elastase breaks down the Outer membrane protein A (OmpA) of E. coli and other Gram-negative bacterium, killing the bacterium carrying the protein.
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In bacteria, secreted elastase breaks down host connective tissue proteins, causing tissue damage and inflammation. As a result, it's considered a virulence factor.
Elastases of the serine protease type preferentially break down peptide bonds on the carboxyl side of small, hydrophobic amino acids such as glycine, alanine, and valine.
Role of human elastase in disease
A1AT
Elastase is inhibited by the acute-phase protein α
1-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. Alpha-1 antitrypsin deficiency (A1AD) leads to uninhibited destruction of elastic fibre by elastase; the main result is emphysema.
Cyclic neutropenia
The
rare disease cyclic neutropenia (also called "cyclic hematopoeiesis") is an autosomal dominant
genetic disorder characterised by fluctuating neutrophil granulocyte counts over 21-day periods. During
neutropenia, patients are at risk for
. In 1999, this disease was linked to disorders in the ELA-2 / ELANE gene.
Other forms of congenital neutropenia also appear to be linked to ELA-2 mutations.
Other diseases
Neutrophil elastase is responsible for the blistering in bullous pemphigoid, a
skin condition, in the presence of
antibody. It may also play a role in the formation of abdominal aortic aneurysms (AAAs) and chronic obstructive pulmonary disease (COPD).
Role of bacterial elastase in disease
Elastase has been shown to disrupt
tight junctions, cause proteolytic damage to tissue, break down
cytokines and
alpha proteinase inhibitor, cleave
antibody A and G (
IgA,
Immunoglobulin G), and cleave both C3bi, a component of the complement system, and CR1, a receptor on
neutrophils for another complement
molecule involved in
phagocytosis. The cleavage of IgA, IgG, C3bi, and CR1 contributes to a decrease of the ability of neutrophils to kill
bacteria by phagocytosis. Together, all these factors contribute to human
pathology.
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