Family M75
Summary for family M75
| Family type peptidase | M75.001 - imelysin (Pseudomonas aeruginosa), MEROPS Accession MER0042581 (peptidase unit: 1-446) |
| Content of family | Peptidase 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 type | Metallo |
| Active site | The 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 specificities | From 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). |
| Inhibitors | Imelysin was completely inhibited by 1mM 1,10-phenanthroline and 1 mM EDTA (Fricke et al., 1999). |
| Molecular structure | Imelysin 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. |
| Clan | MS |
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Distribution of family
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