Summary for peptidase M19.001: membrane dipeptidase

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namemembrane dipeptidase
Other namesantigen 49C, dehydropeptidase I, DPEP1 g.p. (Homo sapiens), dipeptidase 1, leukotriene D4 hydrolase, membrane dipeptidase, microsomal dipeptidase, renal dipeptidase
Domain architecture
MEROPS Classification
Classification Clan MJ >> Subclan (none) >> Family M19 >> Subfamily (none) >> M19.001
Holotypemembrane dipeptidase (Homo sapiens), Uniprot accession P16444 (peptidase unit: 17-385), MERNUM MER0001260
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00228
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.13 (Dipeptidases) >> Peptidase 3.4.13.19
EnzymologyBRENDA database
ActivityMembrane dipeptidase hydrolyses a wide variety of dipeptides regardless of whether the C-terminal residue is in the D or L configuration (<%Hooper, 2004[20040525A436]%>). An that was discovered very early in the study of the enzyme is the hydrolysis of dehydro-dipeptides suchas Gly-dehydroPhe, and the enzyme has been known as dehydrodipeptidase I (<%Campbell, 1970[20040511P974]%>). Activity is not confined to peptides: membrane dipeptidase is the only mammalian beta-lactamase (<%Campbell %etal, 1984[20040831A936]%>) and has also attracted interest for the conversion of leukotriene-D4 to leukotriene-E4 (<%An %etal, 1994[20040510W954]%>).
Activity statushuman: active (Hooper, 2004)
mouse: active (Satoh et al., 1993)
InhibitorsMembrane dipeptidase is inhibited by cilastatin (IC50 0.1 mM), and this compound has been used therapeutically to retard the destruction of beta-lactam antibiotics (Kahan et al., 1983). More potent, aminophosphinic acid inhibitors have also been described (Gurulingappa et al., 2004).
PhysiologyExtracellular catabolism of glutathione. Inactivates leukotriene D4 in the lung. The only mammalian beta-lactamase. Also suggested to maintain oxidising conditions in endoplasmic reticulum
KnockoutGene deletion in mice had no effect on viability or fertility. The mutant mice retain partial ability to convert leukotriene D4 to leukotriene E4 (Habib et al., 1998).
Pharmaceutical relevanceDestroys thienamycin and imipenem in the kidney, and to prevent this, the inhibitor cilastatin is co-administered with the antibiotics.
Other databases TREEFAMhttp://www.treefam.org/family/TF324523
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
DPEP1 16q24.3 ENSG00000174075 1800 DPEP1 179780
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Dpep1 8:E1 ENSMUSG00000019278 13479 MGI:94917