Summary for clan MJ

Summary Alignment Structure Literature
Clan type peptidaseM38.001 - isoaspartyl dipeptidase (metallo-type) (Escherichia coli), MEROPS Accession MER0001495 (peptidase unit: 10-359); PDB accession 1ONW
HistoryMEROPS 3.1 (22 December 1998)
DescriptionWater nucleophile; water bound by two zinc ions ligated by His, His or Asp, Lys or Glu, His, His
Contents of clanClan MJ contains two small families of atypical dipeptidases.
EvidenceA similar protein fold is seen in membrane dipeptidase (M19.001) and isoaspartyl dipeptidase (M38.001).
Catalytic mechanismThese are zinc metallopeptidases containing two metal ions per monomer. The active site residues are His, Asp/His, Glu/Lys, His, His (see the Alignment).
Peptidase activityWe would summarise the peptidase activity of the enzymes in clan MJ as hydrolysis of a variety of dipeptide-sized substrates, without restrictions that are common for other dipeptidases. For example, membrane dipeptidase hydrolyses a wide variety of dipeptides regardless of whether the C-terminal residue is in the D or L configuration (Hooper, 2004). An activity of membrane dipeptidase that was discovered very early in the study of the enzyme is the hydrolysis of dehydro-dipeptides such as GlydehydroPhe, and the enzyme has been known as dehydrodipeptidase I (Campbell, 1970). Activity is not confined to peptides: membrane dipeptidase is the only mammalian beta-lactamase (Campbell et al., 1984) and has also attracted interest for the conversion of leukotriene-D4 to leukotriene-E4 (An et al., 1994). The Acinetobacter dipeptidase AC (M19.003) is more active on Leu-D-Leu than on the normal dipeptide (Adachi & Tsujimoto, 1995). The bacterial beta-aspartyl dipeptidase (M38.001) hydrolyses a variety of beta-aspartyl amino acids, as reviewed by Gary & Clarke (2004).
Protein foldTertiary structures have been determined for peptidases from M19 (Nitanai et al., 2002) and M38 (Jozic et al., 2003). The structures show that members of both families have co-catalytic metal ions. The zinc ions are ligated by five residues, three histidines, an aspartate and a glutamate in family M19 and four histidines and a lysine in family M38. In both families, two of the zinc ligands occur in the motif HXH, which is also present in members of clan MD, which are single zinc peptidases. The common fold consists of a TIM barrel containing eight beta strands (in the order 12345678) surrounded by helices; in family M38 there is a second domain consisting of a beta sheet that caps the top of the barrel..
Homologous non-peptidase familiesFamily M38 contains a number of non-peptidase enzymes, including the urease of Klebsiella (M38.982) and dihydro-orotase (M38.972). It has been pointed out by Gary & Clarke (2004) that the reactions catalysed by beta-aspartyl dipeptidase and dihydro-orotase are clearly analogous.
Activation mechanismThe peptidases in clan MJ are not known to have inactive proenzymes.
Other databases PFAMCL0034


Family Family Type Inhibitor Structure
M19 membrane dipeptidase (Homo sapiens) Yes
M38 isoaspartyl dipeptidase (metallo-type) (Escherichia coli) Yes

Distribution of clan MJ among Kingdoms of Organisms