Protease

From Wikipedia, the free encyclopedia

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain.

1 Classification
2 Occurrence
3 Inhibitors
4 Degradation
5 Protease research
6 References
7 External links

[edit] Classification

There are currently six classes of proteases:

Serine proteases
Threonine proteases
Cysteine proteases
Aspartic acid proteases (e. g., plasmepsin)
Metalloproteases
Glutamic acid proteases

The threonine and glutamic acid proteases were not described until 1995 and 2004, respectively. The mechanism used to cleave a peptide bond involves making an amino acid residue that has the cysteine and threonine (peptidases) or a water molecule (aspartic acid, metallo- and glutamic acid peptidases) nucleophilic so that it can attack the peptide carbonyl group. One way to make a nucleophile is by a catalytic triad, where a histidine residue is used to activate serine, cysteine or threonine as a nucleophile.

[edit] Occurrence

Proteases occur naturally in all organisms and constitute 1-5% of the gene content. These enzymes are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated cascades (e.g., the blood clotting cascade, the complement system, apoptosis pathways, and the invertebrate prophenoloxidase activating cascade). Peptidases can break either specific peptide bonds (limited proteolysis), depending on the amino acid sequence of a protein, or break down a complete peptide to amino acids (unlimited proteolysis). The activity can be a destructive change abolishing a protein's function or digesting it to its principal components; it can be an activation of a function or it can be a signal in a signalling pathway.

Proteases are also a type of exotoxin, which is a virulence factor in bacteria pathogenesis. Bacteria exotoxic proteases destroy extracellular structures. Protease enzymes are also found used extensively in the bread industry in Bread improver.

[edit] Inhibitors

The function of peptidases is inhibited by protease inhibitor enzymes. Examples of protease inhibitors are the class of serpins (serine protease or peptidase inhibitors), incorporating alpha 1-antitrypsin. Other serpins are complement 1-inhibitor, antithrombin, alpha 1-antichymotrypsin, plasminogen activator inhibitor 1 (coagulation, fibrinolysis) and the recently discovered neuroserpin.

Natural protease inhibitors include the family of lipocalin proteins, which play a role in cell regulation and differentiation. Lipophilic ligands, attached to lipocalin proteins, have been found to possess tumor protease inhibiting properties. The natural protease inhibitors are not to be confused with the protease inhibitors used in antiretroviral therapy. Some viruses, with HIV among them, depend on proteases in their reproductive cycle. Thus, protease inhibitors are developed as antiviral means.

[edit] Degradation

Proteases, being themselves proteins, are known to be cleaved by other protease molecules, sometimes of the same variety. This may be an important method of regulation of peptidase activity.

[edit] Protease research

The field of protease research is enormous. Barrett and Rawlings estimated that approximately 8000 papers related to this field are published each year. For a look at current activities and interests of protease researchers, see the International Proteolysis Society web page.

[edit] References

Barrett A.J., Rawlings ND, Woessner JF. The Handbook of Proteolytic Enzymes, 2nd ed. Academic Press, 2003. ISBN 0-12-079610-4.
Hedstrom L. Serine Protease Mechanism and Specificity. Chem Rev 2002;102:4501-4523.
Southan C. A genomic perspective on human proteases as drug targets. Drug Discov Today 2001;6:681-688.
Hooper NM. Proteases in Biology and Medicine. London: Portland Press, 2002. ISBN 1-85578-147-6.
Puente XS, Sanchez LM, Overall CM, Lopez-Otin C. Human and Mouse Proteases: a Comparative Genomic Approach. Nat Rev Genet 2003;4:544-558.
Ross J, Jiang H, Kanost MR, Wang Y. Serine proteases and their homologs in the Drosophila melanogaster genome: an initial analysis of sequence conservation and phylogenetic relationships. Gene 2003;304:117-31.
Puente XS, Lopez-Otin C. A Genomic Analysis of Rat Proteases and Protease Inhibitors. Genome Biol 2004;14:609-622.