Elastase is an enzyme that digests and degrades a number of proteins including elastin, an elastic substance in the lungs and some other organs that supports their structural framework. Elastase is specifically inhibited by alpha-1 antitrypsin
Elastases are a group of proteinases that possess the ability to cleave the important connective tissue protein, elastin. So elastase is named for its ability to digest elastin. Elastin is widely distributed in vertebrate tissue and is particularly abundant in the lungs, arteries, skin and ligaments. It is a connective fiber with elastic properties which allow the tissue to retain its shape after contraction and expansion. Elastin also is primarily composed of four amino acids: glycine, valine, alanine, and proline. Elastin fibers are linked together to make a large, insoluble, resilient cross-linked array and this mesh is notoriously difficult to degrade.
Elastase is a member of the M4 family of Thermolysin-like Neutral zinc-metallo Proteases (TNP). This protease has previously been termed Pseudolysin (EC 184.108.40.206), due to its 49% simillarity to Thermolysin, an M4 metalloprotease secreted by Bacillus thermoproteolyticus. The crystal structure of the mature active enzyme has been solved to 1.5 angstrom resolution. Both proteases, elastase and thermolysin, contain a single zinc atom essential for activity, observed by metal chelation experiments inhibiting enzymatic activity. The active site catalytic residue (Glu-141) for elastase has been determined along with the zinc coordination residues (His-142, His-146, and Glu-166). Elastase also requires calcium ions for stabilization. Additionally, substantial conformational differences were observed when the enzyme was either in the absence of ligand or in the presence of a covalent noncompetitive inhibitor as compared to tight-binding competitive inhibitors. The first group maintains an “open” substrate binding cleft while competitive inhibitors allow the cleft to close.
Elastases can be extremely destructive if not controlled because they can destroy many connective tissue proteins. Under normal physiological conditions, these proteinases are carefully regulated by compartmentalization or by natural circulating plasma proteinase inhibitors. Any imbalance in the levels of the proteinase and antiproteinase leads to extensive tissue destruction. Elastase is produced by over 80% of clinical isolates of P. aeruginosa. Second to the ability to destroy elastin, elastase has the ability to degrade fibrin and collagen barriers as well as inactivate additional host proteins, including alpha-1-proteinase inhibitor, bronchial mucus proteinase inhibitor, lysozyme, complement components, IgG and IgA, along with inactivating signal inflammation cascades. In addition to pulmonary tissue, corneal tissue, urinary tract, and vascular destruction have been linked to elastase activity. Elastase works syngergistically with LasA protease, a serine protease that nicks the elastin and renders it susceptible to other enzymes like elastase. Most of the destructive tissue pathogenesis of P. aeruginosa can be attributed to these secreted enzymes.
Regulation of the production of many of the Pseudomonas aeruginosa virulence factors, including these enzymes, is tightly controlled by a mechanism which monitors bacterial cell density and provides communication between the bacteria by cell-to-cell signaling. Many gramnegative and gram-positive bacteria have developed the ability to sense their environmental conditions and populations through cell-to-cell signaling, also called quorum sensing. This enables the bacteria to secrete the virulence factors only at optimal times for the pathogenesis. The bacteria do this by producing a small molecule called an autoinducer (AI) which is free to diffuse through the cell membrane and away from the cell. In low density populations, the AI diffuses away from the cell into the media and becomes diluted. With increasing bacterial cell density, the concentration of this AI accumulates and reaches a threshold level. The small molecule is now able to bind a transcriptional activator protein, forming a complex which is able to bind DNA sequences upstream of target genes enhancing their transcription. In Pseudomonas aeruginosa, there are two circuit systems that interact to ensure the precise and abundant production of elastase. The autoinducers responsible for elastase synthesis are 3-oxo-C12-HSL (N-[3-oxododecaolyl]-Lhomoserine lactone) and C4-HSL (N-butyrylhomoserine lactone). The AI synthase gene responsible for the first AI (3-oxo-C12-HSL), is lasI and the lasR gene codes for the transcriptional activator protein. Additionally, the las system has been shown to activate the genes necessary for the transport of these enzymes from the cell.
Reference:EMILY NICOLE BOICE. THE ROLE OF THE PROPEPTIDE AND ITS RESIDUES IN ACTIVATION AND SECRETION OF ELASTASE, AN M4 METALLOPROTEASE SECRETED FROM PSEUDOMONAS AERUGINOSA