Elastase
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2008-06-21T13:52:11Z
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[[Image:Elastase.png|right|Elastase]]
[[Image:Protein Crystal Growth Porcine Elastase.jpg|thumb|200px|Protein Crystal Growth Porcine Elastase]]
In [[molecular biology]], '''elastase''' is an [[enzyme]] from the class of ''[[protease]]s'', or [[peptidase]]s, that break down [[protein]]s.
== Forms and classification==
There exist two human [[gene]]s for elastase:
* [[Pancreatic elastase]] (ELA-1)
* [[Neutrophil elastase]] (ELA-2)
Bacterial forms: Organisms such as ''[[Pseudomonas aeruginosa|P. aeruginosa]]'' also produce elastase, and is considered a virulence factor.
== Function ==
Elastase breaks down [[elastin]], an [[Elasticity (physics)|elastic]] [[fiber]] 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]] [[bacterium|bacteria]], and also breaks 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 carboxy 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 reaction|acute phase]] protein [[alpha 1-antitrypsin|α<sub>1</sub>-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|α<sub>1</sub>-antitryspin deficiency]] (A1AD) leads to uninhibited destruction of elastic fiber by elastase; the main result is [[emphysema|pulmonary emphysema]].
=== Cyclic hematopoeiesis ===
The [[rare disease]] [[cyclic neutropenia|cyclic hematopoeiesis]] (also called "cyclic neutropenia") is an [[autosomal dominant]] [[genetic disorder]] characterised by fluctuating [[neutrophil granulocyte]] counts over 21-day periods. During [[neutropenia]], patients are at risk for [[infection]]s. In [[1999]], this disease was linked to disorders in the ELA-2 gene.<ref>{{cite journal |author=Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC |title=Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis |journal=Nat. Genet. |volume=23 |issue=4 |pages=433–6 |year=1999 |pmid=10581030 |doi=10.1038/70544}}</ref> Other forms of congenital [[neutropenia]] also appear to be linked to ELA-2 mutations.
=== Other diseases ===
Neutrophil elastase is responsible for the blistering in [[pemphigoid|bullous pemphigoid]], a skin condition, in the presence of [[antibody|antibodies]].
== The 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|immunoglobuline]] A and G ([[IgA]], [[IgG]]), and cleave both C3bi, a component of the [[complement system]], and CR1, a [[receptor (biochemistry)|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]].
==References==
<references/>
[[Category:EC 3.4.21]]
{{Serine endopeptidases}}
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