Family M75


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family M75

Family type peptidaseM75.001 - imelysin (Pseudomonas aeruginosa), MEROPS Accession MER0042581 (peptidase unit: 1-446)
Content of familyPeptidase family M75 contains metalloendopeptidases.
History Identifier created: MEROPS 7.0 (4 April 2005)
Proteolytic activity was detected in the outer membrane of Pseudomonas aeruginosa by Leopold & Fricke (1997). By use of high-performance liquid chromatography coupled on-line with inductively coupled plasma mass spectrometry, Leopold & Fricke were able to show that the peptidase contained one zinc ion per molecule. From the sequence of internal tryptic peptides (Fricke et al., 1999) it has been possible to detect the sequence in the complete genome of Pseudomonas aeruginosa. The peptidase (M75.001) has been called 'insulin-cleaving membrane protease' and imelysin. Homologues are known from a variety of bacteria.
Catalytic typeMetallo
Active siteThe active site residues have not been identified. However, His201 and Glu204 are completely conserved in the family (see the Alignment) and occur in an HXXE motif that is also found in family M14, where the His and Glu are zinc ligands.
Activities and specificitiesFrom the cleavages of the oxidized insulin B chain, imelysin shows a preference for aromatic hydrophobic amino acids at P1". Imelysin was also shown to cleave fibrinogen (Fricke et al., 1999).
InhibitorsImelysin was completely inhibited by 1mM 1,10-phenanthroline and 1 mM EDTA (Fricke et al., 1999).
Molecular structureImelysin is a membrane protein with the active site outside the cell envelope. On SDS-PAGE the peptidase consisted of a single polypeptide chain with apparent Mr 44,600. The tertiary structure has been solved for homologues from Bacteroides ovatus and Psychrobacter arcticus and shows a fold consisting of two domains, each of which consists of a bundle of four helices. The domains are similar to each other, which implies an ancient gene duplication and fusion event (Xu et al., 2011). The fold of a single domain is similar to that of alginate-binding flagellin, cytochrome C oxidase and some kinases, but unlike that of any peptidase. Consequently, the structure from Bacteroides ovatus is the type structure for clan MS. Neither of the proteins so far crystallized bind metal ions other than by water molecules, and neither is therefore predicted to be a peptidase.
Distribution of family Bacteria details  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses -  
Biological functions
Pharmaceutical and biotech relevanceBecause Pseudomonas aeruginosa is an acute pathogen affecting patients with a compromised immune system, such as cystic fibrosis and burns patients, its peptidases are of potential pharmacological interest.
Statistics for family M75Sequences:329
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
family M75 non-peptidase homologuesnon-peptidase homologue-
family M75 unassigned peptidasesunassignedYes