Metalloproteases
Metalloproteases (formerly: metallopeptidases) are enzymes , the peptide bonds of a protein ( protein ) can cleave ( proteolysis ), in which one molecule of water is consumed ( hydrolysis ) and the water molecule of one or two metal cations is maintained in position. The metal ion is bound to amino acid side residues belonging to the enzyme .
Classification
A first rough classification of metalloproteases can be done according to the type of proteolysis, into metallo endopeptidases (metalloproteinases) and metallo exopeptidases (metallopeptidases in the narrower / newer sense).
Classification according to UniProt / MEROPS
The UniProt Consortium regularly publishes a list of peptidases that categorize these enzymes according to their evolutionary origin. The data in the list are provided with high-quality information and can be called up in the MEROPS database. Closely related molecules are grouped together in families whose identifiers consist of a letter ('M' for metalloproteases) and a number. Families, in turn, belong to clans whose families are related. Clan identifiers have a letter instead of numbers.
There are 54 metalloprotease families in 15 clans (as of 2008), with clan MA with 39 families being of outstanding importance. 19 of these 39 families alone can be assigned to the neutral zinc metallopeptidases.
clan | designation | Exo Endo | metal | Exemplary enzyme | UniProt | Familys |
---|---|---|---|---|---|---|
MA | Neutral zinc metallopeptidases | zinc | Thermolysin ( Bacillus stearothermophilus ) | P06874 | M1-13 M26-7 M30 M32 M34-6 M41 M43 M48 M54 M56-7 M60-1 M64 M66 M72 | |
MC | Zinc carboxypeptidases | Exo | zinc | Carboxypeptidase A1 ( Bos taurus ) | P00730 | M14 |
MD | Exo | zinc | D-Ala-D-Ala-carboxypeptidase ( Streptomyces albus ) | P00733 | M15 M74 | |
ME | Insulinases | Endo | zinc | Pitrilysin ( E. coli ) | P05458 | M16 M44 |
MF | Cytosolic aminopeptidases | Exo | Zinc, manganese | Leucine aminopeptidase ( Bos taurus ) | P00727 | M17 |
MG | Methionine aminopeptidases | Exo | Zinc / cobalt | Methionine aminopeptidase ( Salmonella typhimurium ) | P0A1X6 | M24 |
MH | Exo | 2 zinc | Bacterial leucine aminopeptidase ( Vibrio proteolyticus ) | Q01693 | M18 M20 M28 M42 | |
MJ | Renal dipeptidases | Exo | 2 zinc | Isoaspartyl dipeptidase ( E. coli K12) | P39377 | M19 M38 |
MK | Glycoproteases | Endo | (2 zinc) | Glycoprotease ( Mannheimia typhimurium ) | P36175 | M22 |
MM | Neutral zinc metallopeptidases | Endo | zinc | Site-2 protease ( Homo sapiens ) | O43462 | M50 |
MN | Exo | 2 zinc | D- aminoprotease ( Bacillus subtilis ) | P26902 | M55 | |
MO | Endo | zinc | Lysostaphin ( Staphylococcus simulans ) | P10547 | M23 | |
MP | zinc | JAMM-like protein (Archaea) | A0B7A7 | M67 | ||
MQ | 2 · cobalt | Aminopeptidase T ( Thermus aquaticus ) | P23341 | M29 | ||
M- (not assigned) | M49 M73 M75-6 |
Examples
The following are the main human metalloproteases:
Matrix metalloproteinases
Matrix metalloproteases are a special type of metalloproteases . They can be divided into
In the MEROPS system, matrix metalloproteases are completely contained in the M10A family.
ADAM metalloproteases
In 2006, researchers at Johannes Gutenberg University Mainz published the results of experiments in which it was shown in mice that the plaques that are formed in Alzheimer's disease can be broken down by a certain metalloprotease. The ADAM metalloproteases ADAM10 , a so-called α-secretase , can prevent the formation of such β-amyloid deposits in the brain. It is a metalloprotease that is active in the synapses of healthy nerve cells.
ADAM metalloproteases completely belong to the MEROPS family M12.
Further examples
- Aminopeptidase A (glutamyl aminopeptidase, M1)
- Angiotensin Converting Enzyme (M2)
- Neurolysin (M3)
- MMP20 (M10)
- Meprin A (M12A)
- Neprilysin (M13)
- Carboxypeptidase A1 (M14)
- Insulinase (M16)
- Leucine aminopeptidase (M17)
- Renal Dipeptidase (M19)
- Methionine aminopeptidase 1 (M24)
- CAAX prenyl protease 1 (M48)
Important metalloproteases of other living things:
- Botulinum toxin (botox, M27)
- Tetanus toxin (M27)
- Presequence Protease (M16)
- Bitisgabonine subunit
- Demented
Individual evidence
- ^ Definition of metallopeptidase activity at GeneOntology
- ↑ UniProt: Peptidase families: classification and list of entries.
- ↑ MEROPS: List of clans and families
- ^ Hannes Leischner: Basics oncology. Elsevier GmbH Germany, 2007. ISBN 3437423266 , p. 10
- ↑ U. Schmitt et al .: Over-expression of two different forms of the a-secretase ADAM10 affects learning and memory in mice. Behav Brain Res. 175/2/ 2006 . Pp. 278-284. PMID 17014917