Elastase
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Elastase.png
Elastase
Protein_Crystal_Growth_Porcine_Elastase.jpg
In molecular biology, elastase is an enzyme from the class of proteases (or better peptidases) that break down proteins.
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Forms and classification
There exist two genes for elastase: pancreatic (ELA-1) and neutrophil (ELA-2) elastase. From recent research, it appears that of the two, ELA-1 is not transcribed into a protein [1] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=9175736).
The neutrophil form of elastase (EC 3.4.21.37 (http://www.expasy.ch/cgi-bin/nicezyme.pl?3.4.21.37)) is 218 aminoacids long, with two asparagine-linked carbohydrate chains (see glycosylation). It is present in azurophil granules in the neutrophil cytoplasm. There appear to be two forms of neutrophil elastase, termed IIa and IIb.
Function
Elastase breaks down elastin, an elastic fibre that—together with collagen—determines the mechanical properties of connective tissue. The neutrophil form also breaks down the Outer membrane protein A (OmpA) of E. coli and other Gram negative bacteria, and breaks down Shigella virulence factors.
Genetics
The two ELA genes are located on different chromosomes:
- The gene for ELA-1 is located on chromosome 12q13.
- The gene for ELA-2 is located on chromosome 19p13.3. It consists of five exons.
Role in disease
A1AD
Elastase is inhibited by the acute phase protein α1-antitryspin (A1AT), which binds covalently 1:1 to elastase. α1-antitryspin deficiency (A1AD) leads to uninhibited destruction of elastic fibre by elastase; the main result is pulmonary emphysema.
Cyclic hematopoeiesis
The rare disease 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 infections. In 1999, this disease was linked to disorders in the ELA-2 gene [2] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=10581030). 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 antibodies.
Sources
- OMIM number 130120 (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=130120) and 130130 (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=130130).de:Eleastase