| Peptidase_M48 | |||||||
|---|---|---|---|---|---|---|---|
 | |||||||
| Identifiers | |||||||
| Symbol | Peptidase_M48 | ||||||
| Pfam | PF01435 | ||||||
| Pfam clan | CL0126 | ||||||
| InterPro | IPR001915 | ||||||
| MEROPS | M48 | ||||||
| OPM superfamily | 394 | ||||||
| OPM protein | 4aw6 | ||||||
| Membranome | 317 | ||||||
| |||||||
| Peptidase_M50 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | Peptidase_M50 | ||||||
| Pfam | PF02163 | ||||||
| Pfam clan | CL0126 | ||||||
| InterPro | IPR008915 | ||||||
| MEROPS | M50 | ||||||
| OPM superfamily | 184 | ||||||
| OPM protein | 3b4r | ||||||
| |||||||
Ametalloproteinase, ormetalloprotease, is anyproteaseenzyme whosecatalytic mechanism involves ametal. An example isADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known asmyogenesis.
Most metalloproteases requirezinc, but some usecobalt. The metalion is coordinated to theprotein via threeligands. The ligands coordinating the metal ion can vary withhistidine,glutamate,aspartate,lysine, andarginine.[clarification needed] The fourth coordination position is taken up by alabile water molecule.
Treatment withchelating agents such asEDTA leads to complete inactivation. EDTA is ametal chelator that removes zinc, which is essential for activity. They are also inhibited by the chelatororthophenanthroline.
There are two subgroups of metalloproteinases:
In theMEROPS database peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C,cysteine; G, glutamic acid; M, metallo; S,serine; T,threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise theamino acid as anucleophile and form an acylintermediate - these peptidases can also readily act astransferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activatedwatermolecule. In many instances, the structuralprotein fold that characterises the clan or family may have lost its catalytic activity, yet retained its function inprotein recognition andbinding.[citation needed]
Metalloproteases are the most diverse of the four main protease types, with more than 50 families classified to date. In these enzymes, adivalentcation, usually zinc, activates the water molecule. The metalion is held in place byamino acid ligands, usually three in number. The known metalligands are histidine, glutamate, aspartate or lysine and at least one other residue is required for catalysis, which may play an electrophilic role. Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site.[3] The HEXXHmotif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most oftenvaline or threonine and forms part of the S1' subsite inthermolysin andneprilysin, 'b' is an uncharged residue, and 'c' ahydrophobicresidue.[4]Proline is never found in this site, possibly because it would break thehelicalstructure adopted by thismotif in metalloproteases.[3]
Metallopeptidases from family M48 areintegral membrane proteins associated with theendoplasmic reticulum and Golgi, binding onezinc ion per subunit. Theseendopeptidases include CAAX prenylprotease 1, which proteolytically removes the C-terminalthree residues offarnesylatedproteins.[citation needed]
Metalloproteinase inhibitors are found in numerous marine organisms, including fish, cephalopods, mollusks, algae and bacteria.[5]
Members of the M50 metallopeptidase family include:mammalian sterol-regulatory element binding protein (SREBP) site 2 protease andEscherichia coli protease EcfE, stage IVsporulation protein FB.
