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a pancreatic enzyme that catalyzes the hydrolysis of elastin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/03 00:27:08」(JST)

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Space-filling model of elastase.

Crystals of porcine elastase.

In molecular biology, elastase is an enzyme from the class of proteases (peptidases) that break down proteins.^[1]

Forms and classification

Eight human genes exist for elastase:

Family	Gene symbol		Protein name		EC number
Family	Approved	Previous	Approved	Previous	EC number
chymotrypsin- like	CELA1	ELA1	chymotrypsin-like elastase family, member 1	elastase 1, pancreatic	EC 3.4.21.36
	CELA2A	ELA2A	chymotrypsin-like elastase family, member 2A	elastase 2A, pancreatic	EC 3.4.21.71
	CELA2B	ELA2B	chymotrypsin-like elastase family, member 2B	elastase 2B, pancreatic	EC 3.4.21.71
	CELA3A	ELA3A	chymotrypsin-like elastase family, member 3A	elastase 3A, pancreatic	EC 3.4.21.70
	CELA3B	ELA3B	chymotrypsin-like elastase family, member 3B	elastase 3B, pancreatic	EC 3.4.21.70
chymotrypsin	CTRC	ELA4	chymotrypsin C (caldecrin)	elastase 4	EC 3.4.21.2
neutrophil	ELANE	ELA2	neutrophil elastase	elastase 2	EC 3.4.21.37
macrophage	MMP12	HME	macrophage metalloelastase	macrophage elastase	EC 3.4.24.65

Bacterial forms: Organisms such as P. aeruginosa also produce elastase, and is considered a virulence factor.

Function

Elastase breaks down elastin, an 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 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 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 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 fiber 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 / ELANE gene.^[2] Other forms of congenital neutropenia also appear to be linked to ELA-2 mutations.^{[citation needed]}

Other diseases

Neutrophil elastase is responsible for the blistering in bullous pemphigoid, a skin condition, in the presence of 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 immunoglobuline A and G (IgA, IgG), 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.

References

^ Bieth JG (2001). "[The elastases]". J. Soc. Biol. (in French) 195 (2): 173–9. PMID 11723830.
^ Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC (1999). "Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis". Nat. Genet. 23 (4): 433–6. doi:10.1038/70544. PMID 10581030.

External links

GeneReviews/NCBI/NIH/UW entry on ELANE-Related Neutropenias including cyclic neutropenia

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English Journal

Direct interaction of ONO-5046 with human neutrophil elastase through (1)H NMR and molecular docking.

Feng L, Zhu W, Huang C, Li Y.SourceSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
International journal of biological macromolecules.Int J Biol Macromol.2012 Oct;51(3):196-200. Epub 2012 May 10.
Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as pulmonary emphysema, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and other inflammatory diseases. Therefore, searching for appropriate and potential human neut
PMID 22579959

Proteomic analysis of the soluble and the lysosomal+mitochondrial fractions from rat pancreas: Implications for cerulein-induced acute pancreatitis.

García-Hernández V, Sánchez-Bernal C, Sarmiento N, Viana RA, Ferreira L, Pérez N, Calvo JJ, Sánchez-Yagüe J.SourceDepartment of Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spain.
Biochimica et biophysica acta.Biochim Biophys Acta.2012 Sep;1824(9):1058-67. Epub 2012 Jun 17.
Alterations in protein expression within the initiation phase of acute pancreatitis (AP) might play an important role in the development of this disease, lysosomes being involved in its pathophysiology. The use of pancreatic subcellular fractions in proteomic analysis, simplifies protein maps and he
PMID 22713802