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QuickView for Peptidase M1, membrane alanine aminopeptidase, N-terminal (biogroup)
- Description:
- 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. 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.This group of metallopeptidases belong to the MEROPS peptidase family M1 (clan MA(E)), the type example being aminopeptidase N from Homo sapiens (Human). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.Membrane alanine aminopeptidase is part of the HEXXH+Egroup; it consists entirely of aminopeptidases, spread across a widevariety of species. Functional studies show that CD13/APN catalyzes the removal of single amino acids from the amino terminus of small peptides and probably plays a role in their final digestion; one family member (leukotriene-A4 hydrolase) is known to hydrolyse the epoxide leukotriene-A4to form an inflammatory mediator. This hydrolase has been shown tohave aminopeptidase activity, and the zinc ligands of the M1 familywere identified by site-directed mutagenesis on this enzyme CD13 participates in trimming peptides bound to MHC class II molecules and cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils. CD13 acts as a receptor for specific strains of RNA viruses (coronaviruses) which cause a relatively large percentage of upper respiratory tract infections.
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