SMART: Pfam domain Peptidase

Peptidase_M4

PFAM accession number:	PF01447
Interpro abstract (IPR013856):	Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [ (PUBMED:7674922) ]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [ (PUBMED:7674922) ]. This group of metallopeptidases that belong to the MEROPS peptidase family M4 (thermolysin family, clan MA(E)). The protein fold of the peptidase domain of thermolysin (MEROPS identifier M04.001), is the type example for members of the clan MA. The thermolysin family is composed only of secreted eubacterial endopeptidases. The zinc-binding residues of thermolysin are H-142, H-146 and E-166, with E-143 acting as the catalytic residue. Thermolysin also contains four calcium-binding sites, which contribute to its unusual thermostability. The family also includes enzymes from a number of pathogens, including Legionella and Listeria, and the protein pseudolysin (MEROPS identifier M04.005), all with a substrate specificity for an aromatic residue in the P1' position. Three-dimensional structure analysis has shown that the enzymes undergo a hinge-bend motion during catalysis. Pseudolysin has a broader specificity, acting on large molecules such as elastin and collagen, possibly due to its wider active site cleft [ (PUBMED:7674922) ]. This entry represents a domain found in peptidase M4 family members.
GO function:	metalloendopeptidase activity (GO:0004222)

PFAM accession number:

PF01447

Interpro abstract (IPR013856):

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [ (PUBMED:7674922) ]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [ (PUBMED:7674922) ].

This group of metallopeptidases that belong to the MEROPS peptidase family M4 (thermolysin family, clan MA(E)). The protein fold of the peptidase domain of thermolysin (MEROPS identifier M04.001), is the type example for members of the clan MA. The thermolysin family is composed only of secreted eubacterial endopeptidases. The zinc-binding residues of thermolysin are H-142, H-146 and E-166, with E-143 acting as the catalytic residue. Thermolysin also contains four calcium-binding sites, which contribute to its unusual thermostability. The family also includes enzymes from a number of pathogens, including Legionella and Listeria, and the protein pseudolysin (MEROPS identifier M04.005), all with a substrate specificity for an aromatic residue in the P1' position. Three-dimensional structure analysis has shown that the enzymes undergo a hinge-bend motion during catalysis. Pseudolysin has a broader specificity, acting on large molecules such as elastin and collagen, possibly due to its wider active site cleft [ (PUBMED:7674922) ].

This entry represents a domain found in peptidase M4 family members.

GO function:

metalloendopeptidase activity (GO:0004222)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry Peptidase_M4