Peptidases
| Peptidases | ||
|---|---|---|
| Enzyme classification | ||
| EC, category | 3.4.-.- , hydrolase | |
| Response type | hydrolytic cleavage | |
| Substrate | Peptides | |
| Products | Peptides, amino acids | |
Peptidases (short for peptide bond hydrolases) are enzymes that can cleave proteins or peptides . In doing so , they catalyze the hydrolysis of peptide bonds . Peptidases are also often referred to as proteases , proteinases or proteolytic enzymes , especially when larger proteins are cleaved .
Occurrence and function
Peptidases are ubiquitous; that is, they occur in all tissues and cells of all organisms . A distinction is made between intracellular and extracellular peptidases.
Intracellular peptidases perform a wide variety of tasks in numerous cell compartments . This is how they participate in the post-translational regulation of the protein content of the cell:
- Proteins, including peptidases themselves, are converted into the active state after their production ( see protein biosynthesis ) by splitting off peptide fragments ( limited proteolysis ).
- Signal peptides, which ensure that freshly synthesized proteins reach their correct destination, are split off by signal peptidases .
- Peptidases are involved in the breakdown of antigens , whereby a large, multi-subunit peptidase complex, the proteasome , is involved.
- If proteins are no longer needed or if they are damaged, they are broken down by peptidases in the lysosomes . All eukaryotic cells also have an ATP -dependent proteolytic system that is located in the cytosol .
Extracellularly secreted peptidases are found in animal organisms mainly in the digestive tract , where they catalyze the hydrolytic breakdown of food . They are also found in other extracellular fluids , where they sometimes take on highly specific tasks, such as the peptidases of the blood coagulation system , the complement system and the fibrinolytic system .
By peptidase inhibitors , low molecular weight substances such. B. the anticoagulant rivaroxaban , pepstatin , iodine acetate or phenanthroline can inhibit peptidases in their function.
Peptidases and other enzymes can also be contained in cleaning agents to break down dirt and therefore to increase the effectiveness of these substances.
Importance of peptidases in tumor formation
Peptidases play an important role in the metastasis of malignant tumors . For the development of metastases of malignant solid tumors, it is necessary that tumor cells cross the basement membrane , which consists of collagen (type IV), laminin and heparin sulfate proteoglycans. Peptidases such as serine proteinases , cathepsin proteinases and matrix metalloproteinases play an essential role in overcoming them .
Classification of peptidases
EC nomenclature
Like all other enzymes, peptidases are divided into groups using the so-called EC system . Peptidases belong to class 3 of hydrolases and form subclass 3.4 there. This is in turn divided into 14 sub-subclasses. This nomenclature is based on the type of reaction catalyzed and the active center.
| Sub-subclass | Peptidase type | Number of entries |
| 3.4.11 | Aminopeptidases | 20th |
| 3.4.13 | Dipeptidases | 11 |
| 3.4.14 | Dipeptidyl peptidases | 8th |
| 3.4.15 | Peptidyl dipeptidases | 3 |
| 3.4.16 | Serine carboxypeptidases | 4th |
| 3.4.17 | Metallocarboxypeptidases | 19th |
| 3.4.18 | Cysteine carboxypeptidases | 1 |
| 3.4.19 | Omegapeptidases | 11 |
| 3.4.21 | Serine endopeptidases | 77 |
| 3.4.22 | Cysteine endopeptidases | 28 |
| 3.4.23 | Aspartate endopeptidases | 34 |
| 3.4.24 | Metalloendopeptidases | 70 |
| 3.4.25 | Threonine endopeptidases | 1 |
| 3.4.99 | Endopeptidases of unknown type | 0 |
| Total number | 287 |
Type of proteolytic reaction catalyzed
Since enzymes can catalyze a wide variety of chemical reactions, it makes sense to classify them based on these reactions. A first division of peptidases from an enzymological point of view is that of exopeptidases and endopeptidases .
Exopeptidases cleave the polypeptide chain from the ends. Those who act at the N-terminus are called aminopeptidases (release of a single amino acid ), dipeptidyl peptidases (release of a dipeptide ) or tripeptidyl peptidases (release of a tripeptide ), depending on the fragment split off . Exopeptidases acting at the C-terminus release individual amino acids ( carboxypeptidases ) or dipeptides (peptidyl dipeptidases). In addition, there are exopeptidases that specifically cleave dipeptides (dipeptidases) or remove terminal substituted , cyclized or isopeptide- linked amino acids (omega-peptidases).
Endopeptidases usually cleave at very specific points within the polypeptide chain. A satisfactory classification based on specificity is not possible. Therefore, the subdivision is based on the active center ( see below ). The length of the polypeptide chain to be cleaved can vary within a wide range in the case of endopeptidases. Mostly proteins are the substrates . However, there is also a subgroup of endopeptidases that specialize in shorter peptides as substrates (oligopeptidases).
Type of active center (MEROPS)
The subdivision of the peptidases according to the EC system has weaknesses. Thus the numerous endopeptidases are represented by only six sub-subclasses. Different types of peptidases can be found in the same group. The most serious disadvantage, however, is that structural, evolutionary similarities between the individual enzymes are not taken into account.
To this end, Neil D. Rawlings and Alan J. Barett introduced a new classification scheme, called MEROPS, in 1993, which takes structural aspects and evolutionary relationships based on the amino acid sequence into account.
Like all enzymes, peptidases have an active center that enables the respective reaction - in this case the hydrolysis of peptide bonds. Within these centers, some or groups of amino acids are of crucial importance for functionality. Therefore, peptidases are classified into six groups in the MEROPS database based on the chemical nature of their catalytic, active centers ( see table below ):
| Functional amino acid or active center | Main Products | example | Inhibitor |
| A aspartic acid | Aspartyl proteases | Pepsin , chymosin , cathepsin E. | Pepstatin |
| C cysteine | Cysteine proteases | Papain , Cathepsin K , Caspase , Calpain | Iodoacetate , iodoacetamide , Z-Phe-Phe-diazomethylketone |
| G glutamic acid | Scytalidoglutamic peptidase | 1,2-epoxy-3- (p-nitrophenoxy) propane ( EPNP ) | |
| M Metallo ( metal complex ) | Metalloproteases | Thermolysin , collagenases (in vertebrates), carboxypeptidase A and the like. B. | EDTA , 1,10-phenanthroline |
| S serine | Serine proteases | Chymotrypsin , Plasmin , Thrombin , Trypsin , Granzyme , Kallikrein | APMSF , PMSF , AEBSF , aprotinin , diisopropyl fluorophosphate , α-1-antitrypsin |
| T threonine | Threonyl proteases | Proteasome | (Lactacystin) |
| U Unknown | gpr endopeptidase , prepilin type IV peptidase | none of the above |
Overview of peptidases
Acrosine , aminopeptidase B , bromelain , calpain I , carboxypeptidase A , cathepsin A , cathepsin B , cathepsin D , cathepsin E , cathepsin K , chymotrypsin , collagenase , dipeptidyl peptidase 4 , dispase , elastase , factor IIa , factor Xa , ficeptide , gpr-endopeptide , HIV protease , kallikrein , MBTPS1 , papain , pepsin , plasmin , prepilin type IV peptidase , prolyl oligopeptidase , proteinase K , proteasome , renin , secretases ( alpha , beta and gamma secretase ), thermolysin , thrombin , trypsin , Urokinase
See also
Web links
- MEROPS - the peptidase database (English)
Individual evidence
- ↑ ( Page no longer available , search in web archives ) (PDF)