Family M19


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq Architecture

Summary for family M19

NamePeptidase family M19 (membrane dipeptidase family)
Family type peptidaseM19.001 - membrane dipeptidase (Homo sapiens), MEROPS Accession MER0001260 (peptidase unit: 17-385)
Content of familyPeptidase 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 GlydehydroPhe (Bergmann & Scleich, 1932), an activity unknown for any other peptidase.
Catalytic typeMetallo
Active site residuesH36 D38 E141 H,Y214 H235 
Active siteIn 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 specificitiesDipeptides 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.
InhibitorsMembrane 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 structureThe 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.
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of Klebsiella urease, the type example for clan MJ.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses -  
Biological functionsMembrane 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 relevanceMembrane dipeptidase degrades beta-lactam antibiotics.
Statistics for family M19Sequences:9245
Identifiers with PDB entries:8
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH
PFAM PF01244
SCOP 75079
Peptidases and Homologues MEROPS ID Structure
membrane dipeptidaseM19.001Yes
membrane-bound dipeptidase-2M19.002-
dipeptidase ACM19.003Yes
membrane-bound dipeptidase-3M19.004-
Mername-AA159 peptidaseM19.006-
thermostable dipeptidase (Brevibacillus-type)M19.007Yes
Mername-AA290 peptidaseM19.008-
dipeptidase 2 homologue (rodent)M19.011-
Caul_3875-type dipeptidaseM19.012Yes
GliJ g.p. (Aspergillus fumigatus)M19.013Yes
Mername-AA306 proteinM19.950Yes
CG6154 g.p. (Drosophila melanogaster)M19.A01-
CG42750 g.p. (Drosophila melanogaster)M19.A02-
Family M19 non-peptidase homologuesnon-peptidase homologueYes
Family M19 unassigned peptidasesunassignedYes