Family U72
Summary for family U72
| Family type peptidase | U72.001 - Dop isopeptidase (Mycobacterium tuberculosis), MEROPS Accession MER0397777 (peptidase unit: 1-505) |
| Content of family | Family U72 contains isopeptidase and endopeptidases. |
| History |
Identifier created: MEROPS 9.8 (17 December 2012)
Ubiquitin is a marker for the degradation of proteins by the proteasome (##XT01.001##) in eukaryotes. In bacteria such as Mycobacterium tuberculosis proteins are also targetted for degradation by the bacterial proteasome (T01.005) by being tagged with the protein Pup (prokaryotic ubiquitin-like protein). Both ubiquitin and Pup are attached to a protein by formation of an isopeptide bond between the C-terminal residue of ubiquitin or Pup and the epsilon-amino group of a lysine on the target protein. Pup is ligated to a protein by PafA ('proteasome accessory factor A'; Cerda-Maria et al., 2010). However, the C-terminal residue of Pup is glutamine not glutamic acid, and an extra step is required in which the C-terminal Gln is deamidated by a protein known as Dop ('deamidase of Pup'; Striebel et al., 2009). In addition to acting as a deamidase, Dop also removes Pup from conjugated proteins in a process known as 'depupylation' (Burns et al., 2010). In Rhodococcus, Dop degrades free Pup, which is not recycled, at multiple sites (Yun et al., 2012). |
| Catalytic type | Peptidase of unknown catalytic type |
| Active site | Mutaganesis of four conserved serines and two conserved threonines failed to abolish depupylation activity in Dop, and in the absence of conserved cysteines the catalytic activity remains unknown (Burns et al., 2012). Because the substrate analogue hemagglutinin-Pup-6-diazo-5-oxo-l-norleucine attaches to Asp95, it has been suggested that Dop is an unusual aspartic peptidase in which Asp95 is the nucleophile and Arg206 binds the substrate (Burns et al., 2010). Both residues are well conserved in the family. The active site residues of the structurally-related glutamine synthetase have been determined, and occur in the order Glu, Glu, Asp, Glu, His, Arg and Arg; an alignment between PafA, Dop and YbdK shows these residues to be conserved (Cerda-Maria et al., 2010). |
| Activities and specificities | In releasing Pup from conjugates, Dop acts as an isopeptidase (Imkamp et al., 2010). In degradation of Pup, Dop acts as an endopeptidase (Yun et al., 2012). |
| Molecular structure | No tertiary structure has been determined for any member of family U72. Both Dop and PafA have been shown to be related to members of the superfamily containing gamma-glutamylcysteine synthetase and glutamine synthetase (Iyer et al., 2008), for which structures are known. The structure of Escherichia coli carboxylate-amine ligase YbdK was used to construct a theoretical model of Dop (Burns et al., 2012). |
| Clan | unassigned |
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Distribution of family
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