Family M36

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family M36

NamePeptidase family M36 (fungalysin family)
Family type peptidaseM36.001 - fungalysin (Aspergillus fumigatus), MEROPS Accession MER0001400 (peptidase unit: 246-634)
Content of familyFamily M36 contains endopeptidases.
History Identifier created: Proteolysis in Cell Function, pp13-21, IOS Press, Amsterdam (1997)
Family M36 includes a number of endopeptidases from pathogenic fungi. These endopeptidases appear to be adapted for cleaving extracellular matrix proteins such as elastin and keratin.
Catalytic typeMetallo
Active site residuesH429 E430 H433 
Active sitePeptidases in family M36 contain the HEXXH motif found in metallopeptidases from clan MA. One zinc ion is tetrahedrally bound by the two histidines in the motif, a third residue as yet undetermined in this family, and a water molecule that acts as a nucleophile during catalysis. The third ligand has been suggested to be Glu459 (Kolattukudy & Sirakova, 2004), but could be any of a number of conserved Glu, Asp or His residues C-terminal to the HEXXH motif (see the Alignment). Glu459 occurs in an EXXXD motif, similar to a motif present in members of family M4, in which the aspartate is also an active site residue.
Activities and specificitiesFungalysin (M36.001) can hydrolyse laminins, elastin and collagen, with a preference for cleavage on the amino side of hydrophobic residues with bulky side-chains. Peptidases from Microsporum canis hydrolyse keratin (Brouta et al., 2001).
InhibitorsTypical metal chelators such as EDTA and 1,10-phenanthroline are inhibitory. Phosphoramidon (10-50 micrograms/ml) is also inhibitory (Monod et al., 1993).
Molecular structureNo tertiary structure has been determined, but from the presence of the HEXXH and EXXXD motifs, the fold is predicted to be similar to that of members of family M4. Hence family M36 is included in subclan MA(E) of clan MA. Fungalysin is a secreted protein with an N-terminal signal peptide followed by a 227-residue propeptide.
ClanMA
SubclanMA(E)
Basis of clan assignmentPredicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH
Distribution of family Bacteria details  
Archaea -  
Protozoa details  
Fungi details  
Plants -  
Animals -  
Viruses -  
Biological functionsFungalysin is secreted when Aspergillus fumigatus invades the lungs of immunocompromised animals (Markaryan et al., 1994), and probably helps break down proteinaceous structural barriers.
Pharmaceutical and biotech relevanceAspergillus fumigatus causes the pulmonary disease aspergillosis, and is able to grow on lung tissue. A solid lesion known as an aspergilloma can grow in a lung cavity, especially following recovery from tuberculosis. Sometimes aspergillosis can be invasive. The keratinolytic metallopeptidase from Microsporum canium has been used as a vaccine (Vermout et al., 2004).
Statistics for family M36Sequences:775
Identifiers:1
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
fungalysinM36.001Yes
family M36 non-peptidase homologuesnon-peptidase homologue-
family M36 unassigned peptidasesunassigned-