Human neutrophil elastase
Encyclopedia
Neutrophil elastase also known as ELA2 (elastase 2, neutrophil) is a serine proteinase in the same family as chymotrypsin
and has broad substrate specificity. Secreted by neutrophils during inflammation, it destroys bacteria and host tissue.
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 dimension conformation of the folded protein. The gene encoding neutrophil elastase, ELA2, consists of five exon
s. It is one of the two human forms of elastase
.
The neutrophil form of elastase is 218 amino acid
s 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.
, which resides on chromosome 19.
and severe congenital neutropenia (SCN). This gene is clustered with other serine protease gene family members, azurocidin 1 and proteinase 3 genes, at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation.
or emphysematous changes. This involves breakdown of the lung structure and increased airspaces. Mutations of the ELA2 gene cause severe congenital neutropenia, which is a failure of neutrophils to mature.
with Alpha 2-antiplasmin
.
Chymotrypsin
Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...
and has broad substrate specificity. Secreted by neutrophils during inflammation, it destroys bacteria and host tissue.
As with other serine proteinases it contains a charge relay system composed of the catalytic triad of histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
, aspartate, and serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
residues that are dispersed throughout the primary sequence of the polypeptide but that are brought together in the three dimension conformation of the folded protein. The gene encoding neutrophil elastase, ELA2, consists of five exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
s. It is one of the two human forms of elastase
Elastase
In molecular biology, elastase is an enzyme from the class of proteases that break down proteins.- Forms and classification:There exist eight human genes for elastase:Bacterial forms: Organisms such as P...
.
The neutrophil form of elastase is 218 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s long, with two asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
-linked carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
chains (see glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
). It is present in azurophil
Azurophil
An azurophil is an object readily stained with an azure dye. Azurophils include certain cytoplasmic granules in white blood cells and hyperchromatin, imparting a burgundy or merlot coloration. Neutrophils in particular are known for containing azurophils loaded with a wide variety of...
granules in the neutrophil
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. There appear to be two forms of neutrophil elastase, termed IIa and IIb.
Gene
In humans, neutrophil elastase is encoded by the ELA2 geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, which resides on chromosome 19.
Function
Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes that encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Elastase 2 hydrolyzes proteins within specialized neutrophil lysosomes, called azurophil granules, as well as proteins of the extracellular matrix following the protein's release from activated neutrophils. Elastase 2 may play a role in degenerative and inflammatory diseases by its proteolysis of collagen-IV and elastin of the extracellular matrix. This protein degrades the outer membrane protein A (OmpA) of E. coli as well as the virulence factors of such bacteria as Shigella, Salmonella and Yersinia. Mutations in this gene are associated with cyclic neutropeniaNeutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
and severe congenital neutropenia (SCN). This gene is clustered with other serine protease gene family members, azurocidin 1 and proteinase 3 genes, at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation.
Clinical significance
Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause emphysemaEmphysema
Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. It is included in a group of diseases called chronic obstructive pulmonary...
or emphysematous changes. This involves breakdown of the lung structure and increased airspaces. Mutations of the ELA2 gene cause severe congenital neutropenia, which is a failure of neutrophils to mature.
Interactions
Neutrophil elastase has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Alpha 2-antiplasmin
Alpha 2-antiplasmin
Alpha 2-antiplasmin is a serine protease inhibitor responsible for inactivating plasmin, an important enzyme that participates in fibrinolysis and degradation of various other proteins...
.