Family M19
Summary for family M19
| Name | Peptidase family M19 (membrane dipeptidase family) |
|---|
| Family type peptidase | M19.001 - membrane dipeptidase (Homo sapiens), MEROPS Accession MER0001260 (peptidase unit: 17-385) |
| Content of family | Peptidase family M19 contains dipeptidases. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
Membrane dipeptidase (M19.001) was originally described as a dehydropeptidase because of its ability to cleave Gly dehydroPhe (Bergmann & Scleich, 1932), an activity unknown for any other peptidase. |
| Catalytic type | Metallo |
| Active site residues | H36 D38 E141 H,Y214 H235 |
| Active site | In membrane dipeptidase, two zinc ions are bound by His20, Asp22, Glu125, His198 and His219, with Glu125 binding both metal ions. Although all five zinc ligands are conserved, dipeptidase AC from Klebsiella (M19.003) is suggested to contain only one zinc ion per molecule (Adachi & Tsujimoto, 1995). |
| Activities and specificities | Dipeptides and beta-lactams are cleaved. Membrane dipeptidase and dipeptidase AC accept D-amino acids in the P1" position, which is unusual for any peptidase. The substrate GlydehydroPhe is cleaved only by membrane dipeptidase and is useful as a specific substrate. Dehydropeptidases are not cleaved by dipeptidase AC. |
| Inhibitors | Membrane dipeptidase is inhibited by cilastatin, which is usually administered with the antibiotic Imipenem that is a substrate for the enzyme. However, the homologous bacterial dipeptidases are unaffected by cilastatin. |
| Molecular structure | The tertiary structure of human membrane dipeptidase has been determined (Nitanai et al., 2002). The peptidase exists as a homodimer, with two disulfide bonds linking the monomers. Each monomer contains an eight-stranded beta barrel surrounded by helices. The active site is in the centre of the barrel. The structure is similar to that of members of family M38, including the non-peptidase homologues urease and dihydro-orotase. Hence families M19 and M38 are included in the same clan, MJ. Membrane dipeptidase is a glycoprotein. |
| Clan | MJ |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of Klebsiella urease, the type example for clan MJ. |
| Biological functions | Membrane dipeptidase is located at the renal brush border membrane, lung, intestine and pancreatic zymogen granules, where it is attached by a glycosylphosphatidylinositol anchor. It is synthesized with a signal peptide and a C-terminal hydrophobic domain which are removed by post-translational processing. Membrane dipeptidase inactivates leukotriene D4 by converting it to leukotriene E4; it also acts in the degradation of extracellular glutathione, cleaving the Cys-Gly dipeptide after glutamate has been removed by gamma-glutamyl transpeptidase. |
| Pharmaceutical and biotech relevance | Membrane dipeptidase degrades beta-lactam antibiotics. |
| Statistics for family M19 | Sequences: | 9245 |
| Identifiers: | 13 |
| Identifiers with PDB entries: | 8 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| membrane dipeptidase | M19.001 | Yes |
| membrane-bound dipeptidase-2 | M19.002 | - |
| dipeptidase AC | M19.003 | Yes |
| membrane-bound dipeptidase-3 | M19.004 | - |
| Mername-AA159 peptidase | M19.006 | - |
| thermostable dipeptidase (Brevibacillus-type) | M19.007 | Yes |
| Mername-AA290 peptidase | M19.008 | - |
| dipeptidase 2 homologue (rodent) | M19.011 | - |
| Caul_3875-type dipeptidase | M19.012 | Yes |
| GliJ g.p. (Aspergillus fumigatus) | M19.013 | Yes |
| Mername-AA306 protein | M19.950 | Yes |
| CG6154 g.p. (Drosophila melanogaster) | M19.A01 | - |
| CG42750 g.p. (Drosophila melanogaster) | M19.A02 | - |
| Family M19 non-peptidase homologues | non-peptidase homologue | Yes |
| Family M19 unassigned peptidases | unassigned | Yes |
