Family M29


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family M29

NamePeptidase family M29 (aminopeptidase T family)
Family type peptidaseM29.001 - aminopeptidase T (Thermus aquaticus), MEROPS Accession MER0001285 (peptidase unit: 1-408)
Content of familyFamily 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 typeMetallo
Active site residuesE250 E316 H345 Y352 H376 D378 
Active sitePeptidases 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 specificitiesAminopeptidase 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).
InhibitorsAminopeptidase 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 structureThe 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.
Basis of clan assignmentProtein fold and active site residues are not known for any members of this family.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsAminopeptidases 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 relevanceAminopeptidase 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 M29Sequences:2614
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
aminopeptidase TM29.001Yes
aminopeptidase II (Bacillus-type)M29.002-
PepS aminopeptidaseM29.004-
aminopeptidase S (Staphylococcus-type)M29.005Yes
family M29 non-peptidase homologuesnon-peptidase homologue-
family M29 unassigned peptidasesunassigned-