Family M17


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

Summary for family M17

NamePeptidase family M17 (leucyl aminopeptidase family)
Family type peptidaseM17.001 - leucine aminopeptidase 3 (Bos taurus), MEROPS Accession MER0001235 (peptidase unit: 33-519)
Content of familyPeptidase family M17 contains aminopeptidases.
History Identifier created: Biochem.J. 290:205-218 (1993)
Leucyl aminopeptidase (M17.001) was the first metallopeptidase to be discovered that possesses two metal ions essential for catalysis (Burley et al., 1990).
Catalytic typeMetallo
Active site residuesK282 D287 K294 D305 D364 E366 R368 
Active siteThe metal ions are described as 'co-catalytic', and a number of other metallopeptidase families with co-catalytic metal ions are now known, including M20, M24 and M28. In all metallopeptidases so far known, each metal ion is divalent and is co-ordinated by three amino acid side chains and a water molecule. Because one amino acid residue binds both metals, metallopeptidases with co-catalytic metal ions have five amino acid metal ligands rather than six, hence the metal ions are pentahedrally co-ordinated. The metal ions are both zinc in mammalian leucyl aminopeptidase but are manganese in bacterial leucyl aminopeptidase (M17.003, also known as aminopeptidase A). One ion is bound by the carboxylates of Asp255, Asp332 and Glu334 and the second by the amino group of Lys250, and the carboxylates of Asp273 and Glu334. Glu334 binds both metal ions, and the backbone carbonyl group of Asp332 coordinates both metals. A single water molecule bridges both metal ions. Lys262 is important for the stabilization of the substrate-enzyme complex, which is known as a gem-diolate.
Activities and specificitiesLeucyl aminopeptidase is maximally active between pH 9 and 9.5. Any N-terminal amino acid can be released from dipeptides and polypeptides, although there is a preference for leucine. Bonds with proline in P1" are not cleaved. A typical test substrate is Leu-NHPhNO2.
InhibitorsLeucyl aminopeptidase is inhibited by bestatin and amastatin.
Molecular structureLeucyl aminopeptidase exists naturally as a homohexamer, with the active sites lining a central disc-shaped cavity. The tertiary structure of cattle leucyl aminopeptidase has been solved revealing a two-domain structure, with the active site of the peptidase in the C-terminal domain. The two domains are unrelated to each other, unlike the domains of methionyl aminopeptidase (family M24). The C-terminal domain shows some structural resemblance to carboxypeptidase A (family M14) and peptidases from families M20 and M28, and the four families are considered to be homologous (Artymiuk et al., 1992). It is unlikely that the common ancestor was a metallopeptidase, however, because the positions of the metal ligands are not conserved between families. Peptidase activity is assumed to have developed independently in each family. For this reason, family M17 is placed in a different clan (MF) to that of family M14 (MC) and families M20 and M28 (both of which are in clan MH).
Basis of clan assignmentType family of clan MF.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses -  
Biological functionsMammalian leucyl aminopeptidase is cytosolic and involved in the breakdown of peptide products of intracellular proteinases. It is one of the enzymes that trims proteasome-produced peptides for class I antigen presentation and its gene is promoted by interferon gamma (Beninga et al., 1998). Bacterial leucyl aminopeptidase is also intracellular, but the plant form is located in the chloroplast and is synthesized with an N-terminal targeting peptide.
Statistics for family M17Sequences:5746
Identifiers with PDB entries:6
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH 3.40.630.10
PFAM PF00883
SCOP 53201
Peptidases and Homologues MEROPS ID Structure
leucine aminopeptidase 3M17.001Yes
leucyl aminopeptidase (plant-type)M17.002Yes
PepA aminopeptidaseM17.003Yes
PepB aminopeptidaseM17.004-
Mername-AA040 peptidaseM17.005-
leucyl aminopeptidase-1 (Caenorhabditis-type)M17.006-
M17 aminopeptidase (Plasmodium spp.)M17.008-
aminopeptidase yspII (Schizosaccharomyces sp.)M17.009-
leucyl aminopeptidase (Bacillus-type)M17.010-
leucine aminopeptidase (Fasciola-type)M17.011-
PwLAP aminopeptidaseM17.012-
cysteinylglycinase (Treponema denticola)-like peptidaseM17.013-
LAPTc aminopeptidaseM17.014-
aminopeptidase pepZ (Staphylococcus sp.)M17.015-
aminopeptidase A/I (Helicobacter-type)M17.016Yes
similar to cytosol aminopeptidase (Rattus norvegicus)M17.950-
At4g30920 (Arabidopsis thaliana)M17.A01-
At4g30910 (Arabidopsis thaliana)M17.A02-
At2g24200 (Arabidopsis thaliana)M17.A03-
CG7340 protein (Drosophila melanogaster)M17.A04-
ZK353.6 (Caenorhabditis elegans)M17.A05Yes
family M17 non-peptidase homologuesnon-peptidase homologue-
family M17 unassigned peptidasesunassignedYes