العربية
中国
Français
Deutsch
Ελληνική
हिन्दी
Italiano
日本語
Português
Русский
EspañolPROTEASE
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.
There are six classes of proteases that are currently known:
★ 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.
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.
PROTEASES (proteinases) are large group of ENZYMES - enzymes are the
protein molecules which play the role of biocatalysts in the organism,
they catalyse the reactions of all metabolic processes. Enzymes are
divided into classes, one of which is the class of HYDROLASES - these
enzymes catalyse the reaction of hydrolysis of various bonds (peptide
bonds, ester bonds etc.) with the participation of a water molecule.
PROTEOLYTIC ENZYMES (PROTEASES) belong to the class of HYDROLASES.
Proteases are involved in splitting the peptide bonds which link the amino
acid residues (elementar units of PROTEINS). Thus proteins are the
SUBSTRATES for proteases. These enzymes "digest" long protein chain to
shorter fragments. Some of them can detach the terminal amino acids from
the protein chain (EXOPEPTIDASES - like aminopeptidases, carboxipeptidase
A), the others "attack" internal peptide bonds of a protein (ENDOPEPTIDASES
- like trypsin, chymotrypsin, pepsin, papain, elastase).
Proteases are divided into four major groups according to the character of
their active site (catalytic site) and conditions of action: serine
proteinases, cysteine (thiol) proteinases, aspartic proteinases and
METALLOPROTEINASES. Attachment of a protease to a certain group depends on
the structure of catalytic site and the amino acid (as one of the
constituents) essential for its activity.
Proteases are everywhere and they are involved in various metabolic
processes. Acid proteases secreted into the stomach (such as PEPSIN) and
serine proteases present in duodeum (TRYPSIN, CHYMOTRYPSIN), enable us to
digest the protein in food, proteases present in blood serum (THROMBIN,
PLASMIN, HAGEMAN FACTOR etc.) play important role in blood clotting, as well
as lysis of the clots, and the correct action of the immune system. Other
proteases are present in leukocytes (ELASTASE, CATHEPSIN G) and play several
different roles in metabolic control. Proteases determine the lifetime of
other proteins playing important physiological role like hormones,
antibodies, or other enzymes - this is one of the fastest "switching on"
and "switching off" regulatory mechanisms in the physiology of an organism.
By complex cooperative action the proteases may proceed as "cascade"
reactions which result in amplification of the organism response to the
physiological signal, and make this response very fast.
The function of peptidases is inhibited by protease inhibitor enzymes. Examples of protease inhibitors are the class of serpins (''ser''ine ''p''rotease or ''p''eptidase ''in''hibitors), 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.
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.
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.
★ 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.
★ In-Gel Protease Digestion of Proteins for Mass Spectrometry
★ International Proteolysis Society
★ Merops - the peptidase database
★ List of protease inhibitors
★
| Contents |
| Classification |
| Occurrence |
| Inhibitors |
| Degradation |
| Protease research |
| References |
| External links |
Classification
There are six classes of proteases that are currently known:
★ 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.
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.
PROTEASES (proteinases) are large group of ENZYMES - enzymes are the
protein molecules which play the role of biocatalysts in the organism,
they catalyse the reactions of all metabolic processes. Enzymes are
divided into classes, one of which is the class of HYDROLASES - these
enzymes catalyse the reaction of hydrolysis of various bonds (peptide
bonds, ester bonds etc.) with the participation of a water molecule.
PROTEOLYTIC ENZYMES (PROTEASES) belong to the class of HYDROLASES.
Proteases are involved in splitting the peptide bonds which link the amino
acid residues (elementar units of PROTEINS). Thus proteins are the
SUBSTRATES for proteases. These enzymes "digest" long protein chain to
shorter fragments. Some of them can detach the terminal amino acids from
the protein chain (EXOPEPTIDASES - like aminopeptidases, carboxipeptidase
A), the others "attack" internal peptide bonds of a protein (ENDOPEPTIDASES
- like trypsin, chymotrypsin, pepsin, papain, elastase).
Proteases are divided into four major groups according to the character of
their active site (catalytic site) and conditions of action: serine
proteinases, cysteine (thiol) proteinases, aspartic proteinases and
METALLOPROTEINASES. Attachment of a protease to a certain group depends on
the structure of catalytic site and the amino acid (as one of the
constituents) essential for its activity.
Proteases are everywhere and they are involved in various metabolic
processes. Acid proteases secreted into the stomach (such as PEPSIN) and
serine proteases present in duodeum (TRYPSIN, CHYMOTRYPSIN), enable us to
digest the protein in food, proteases present in blood serum (THROMBIN,
PLASMIN, HAGEMAN FACTOR etc.) play important role in blood clotting, as well
as lysis of the clots, and the correct action of the immune system. Other
proteases are present in leukocytes (ELASTASE, CATHEPSIN G) and play several
different roles in metabolic control. Proteases determine the lifetime of
other proteins playing important physiological role like hormones,
antibodies, or other enzymes - this is one of the fastest "switching on"
and "switching off" regulatory mechanisms in the physiology of an organism.
By complex cooperative action the proteases may proceed as "cascade"
reactions which result in amplification of the organism response to the
physiological signal, and make this response very fast.
Inhibitors
The function of peptidases is inhibited by protease inhibitor enzymes. Examples of protease inhibitors are the class of serpins (''ser''ine ''p''rotease or ''p''eptidase ''in''hibitors), 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.
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.
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.
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.
External links
★ In-Gel Protease Digestion of Proteins for Mass Spectrometry
★ International Proteolysis Society
★ Merops - the peptidase database
★ List of protease inhibitors
★
This article provided by Wikipedia. To edit the contents of this article, click here for original source.
psst.. try this: add to faves
