Family M29
Summary for family M29
| Name | Peptidase family M29 (aminopeptidase T family) |
|---|
| Family type peptidase | M29.001 - aminopeptidase T (Thermus aquaticus), MEROPS Accession MER0001285 (peptidase unit: 1-408) |
| Content of family | Family M29 contains aminopeptidases. |
| History |
Identifier created: Methods Enzymol. 248:183-228 (1995)
The family includes aminopeptidases from thermophilic bacteria such as aminopeptidase T (M29.001) from Thermus aquaticusand PepS aminopeptidase (M29.004) from Streptococcus thermophilus. |
| Catalytic type | Metallo |
| Active site residues | E250 E316 H345 Y352 H376 D378 |
| Active site | Peptidases in family M29 have cocatalytic metal ions. In aminopeptidase S (M29.005), the metal is cobalt and the ligands are Glu253, Glu319, His348, His381 and Asp383. Tyr355 has been predicted to be a catalytic residue (see the Alignment; Odintsov et al., 2005). Aminopeptidase APII (M29.002) has also been shown to possess cocatalytic cobalt ions (Kuo et al., 2003, Stoll et al., 1976). The only other family of metallopeptidases with cocatalytic cobalt ions is M24. |
| Activities and specificities | Aminopeptidase T is thermostable to 70 degrees Celsius. Thermostability is not a characteristic of the family: aminopeptidases APII and APIII are thermolabile. Aminopeptidase T is an aminopeptidase with a broad substrate specificity, but preferentially releases Leu, Val, Phe or Tyr. It can release Pro but is unable to cleave peptides with Pro in P1". Leu-NHPhNO2 is the usual synthetic substrate Motoshima & Kaminogawa, 2004. PepS aminopeptidase (M29.004) releases Arg and Trp from peptides, and Gly and Ala from dipeptides; it does not hydrolyse Lys-NHPhNO2, a substrate of PepN aminopeptidase (M01.005) (Rul, 2004). |
| Inhibitors | Aminopeptidase T is inhibited by the general metal chelators EDTA and 1,10-phenanthroline, activity can be restored by the addition of cobalt but not zinc. The general aminopeptidase inhibitors amastatin and bestatin (the latter only at high concentrations) are also inhibitory. Reducing agents such as mercaptoethanol and dithiothreitol are also inhibitory, although no cysteine residue is conserved in the family. |
| Molecular structure | The tertiary structure for aminopeptidase S from Staphylococcus aureus (M29.005) has been determined. The structure is unlike that of any other protein, and aminopeptidase S is the type example for clan MQ. Aminopeptidases T, APII and APIII exist naturally as non-disulfide-linked homodimers, but the PepS aminopeptidase is monomeric. |
| Clan | MQ |
| Basis of clan assignment | Protein fold and active site residues are not known for any members of this family. |
| Biological functions | Aminopeptidases T, APII and APIII are cytoplasmic enzymes, presumably with a house-keeping function. The PepS aminopeptidase is induced when certain strains of Streptococcus thermophilus are grown on particular media, such as milk. |
| Pharmaceutical and biotech relevance | Aminopeptidase T is available commercially and is used for N-terminal sequence determination. PepS aminopeptidase is isolated from the lactic acid bacterium Streptococcus thermophilus, which is used in the dairy industry. Hydrolysis of certain peptides can affect their bitter taste, so the peptidase may be important in cheese-making. |
| Statistics for family M29 | Sequences: | 6498 |
| Identifiers: | 4 |
| Identifiers with PDB entries: | 2 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
