Family T2
Summary for family T2
| Family type peptidase | T02.001 - glycosylasparaginase precursor (Homo sapiens), MEROPS Accession MER0003299 (peptidase unit: 206-346) |
| Content of family | Peptidase family T2 contains a set of the N-terminal nucleophile hydrolases, including the glycosylasparaginase precursor. |
| History |
Identifier created: MEROPS 5.00 (20 April 2000)
Family T2 was first recognised in MEROPS in 2000. The only peptidase reactions known to be catalysed by proteins in the family at the time were autolytic cleavage events. In these reactions, precursor proteins converted themselves into active enzymes that were not peptidases. However, the mature taspase (T02.004) is an endopeptidase (Hsieh et al., 2003). |
| Catalytic type | Threonine |
| Active site residues | T206 |
| Active site | Processing of the precursor proteins exposes an N-terminal threonine residue that is the nucleophile in catalysis (Aronson, 2004). All peptidases of this family require (1) the side-chain of an N-terminal amino acid to act as a nucleophile, and (2) the free alpha amino acid group becomes the base and helps to polarize the side-chain nucleophile. |
| Activities and specificities | All the peptidases in this family are endopeptidases. Examples are found in bacteria, archaea and eukaryotes, but not in viruses. The signal peptide of the precursor is removed by intramolecular autoproteolytic cleavage, producing a two-chain heterodimer and liberating the N-terminal nucleophilic Thr responsible for hydrolytic activity. Once converted to their active forms the peptidases in family T2 vary in the reaction that they catalyse. Examples are glycosylasparaginase (EC 3.5.1.26) which hydrolyses the GlcNAc Asn (the natural linkage structure between protein and carbohydrate in Asn-linked glycoproteins) and taspase-1 which cleaves aspartyl bonds DGADD and DGVDD in the product of the Mixed-Lineage Leukaemia (MLL) gene (Hsieh et al., 2003). |
| Inhibitors | An inhibitor of glycosylasparaginase is 5-diazo-4-oxonorvaline (DON) which has been shown to react with the N-terminal threonine of the beta subunit (Tarentino & Maley, 1969; Kaartinen et al., 1991). |
| Molecular structure | The tertiary structure of the enzymes of the glycosylasparaginase precursor family is typical of the "N-terminal nucleophile" hydrolases in clan PB. It is made up of four layers. There are two anti-parallel beta sheets that lie between two layers of alpha helices, forming an alpha-beta-beta-alpha sandwich (Brannigan et al., 1995). The active-site is located in a narrow pocket between the two beta sheets. |
| Clan | PB |
| Subclan | PB(T) |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of archaean proteasome subunit B, the type example of clan PB. |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| glycosylasparaginase precursor | T02.001 | Yes |
| isoaspartyl dipeptidase (threonine type) | T02.002 | Yes |
| taspase-1 | T02.004 | Yes |
| Chryseobacterium meningosepticum-type N4-(beta-N-acetylglucosaminyl)-L-asparaginase | T02.007 | Yes |
| At5g08100 (Arabidopsis thaliana) | T02.A01 | Yes |
| At3g16150 (Arabidopsis thaliana) | T02.A02 | Yes |
| CG10474 protein (Drosophila melanogaster) | T02.A04 | - |
| K01G5.9 g.p. (Caenorhabditis elegans) | T02.A05 | - |
| SPAC823.09c g.p. (Schizosaccharomyces pombe) | T02.A06 | - |
| Family T02 non-peptidase homologues | non-peptidase homologue | - |
| Family T02 unassigned peptidases | unassigned | - |
