Family M8


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

Summary for family M8

NamePeptidase family M8 (leishmanolysin family)
Family type peptidaseM08.001 - leishmanolysin (Leishmania major), MEROPS Accession MER0001165 (peptidase unit: 101-602)
Content of familyPeptidase family M8 contains the metallo-endopeptidase leishmanolysin and its homologues.
History Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic typeMetallo
Active site residuesH264 E265 H268 H334 M345 
Active siteLeishmanolysin is a zinc metallopeptidase with the zinb-binding HEXXH motif, and a more C-terminal His residue that is the third ligand of zinc.
Activities and specificitiesLeishmanolysin is an endopeptidase. The P1" residue at a site of cleavage is often Leu, Ile or Val, and Lys in P3" or P4" may be favourable.
InhibitorsLeishmanolysin is inhibited by metal-chelating agents like 1,10-phenanthroline at millimolar concentrations, but not by EDTA or phosphoramidon. Z-Tyr-Leu-hydroxamate inhibits leishmanolysin in the high micromolar range. Leishmanolysin itself has a neutral pH optimum, but some homologues have been reported to show acidic pH optima.
Molecular structureThe tertiary structure of leishmanolysin (Schlagenhauf et al., 1998) places family M8 in the subclan of metzincins, MA(M). The metzincins contain a highly-conserved methionine residue, and in leishmanolysin this is 11 residues C-terminal to the histidine third ligand. Leishmanolysin occurs mainly as a heavily-glycosylated protein that is attached to the outer membrane of the promastigate stage of the protozoan by a glycosylphosphatidylinositol anchor. There is a proenzyme that appears to contain a "cysteine-switch" sequence similar to those in other families of metzincins (Macdonald et al., 1995).
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of thermolysin, the type example for clan MA.
Distribution of family Bacteria details  
Archaea -  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses -  
Biological functionsLeishmanolysin is the most abundant surface protein of leishmania promastigotes, and may well contribute to the virulence of the organism (Yao et al. 2003). The enzyme has been suggested to facilitate migration of the organism through the extracellular matrix of the host (McGwire et al., 2003).
Pharmaceutical and biotech relevanceLeishmanolysin is a target for inhibitors that might have therapeutic value in leishmaniasis.
Statistics for family M8Sequences:2563
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH
PFAM PF01457
SCOP 55499
Peptidases and Homologues MEROPS ID Structure
invadolysin (invertebrate-type)M08.002-
LMLN2 g.p. (Homo sapiens)M08.005-
At5g42620 (Arabidopsis thaliana)M08.A01-
T13B5.9 g.p. (Caenorhabditis elegans)M08.A02-
DDB_G0280125 g.p. (Dictyostelium discoideum)M08.A03-
DDB_G0282305 g.p. (Dictyostelium discoideum)M08.A04-
DDB_G0286533 g.p. (Dictyostelium discoideum)M08.A05-
sigB g.p. (Dictyostelium discoideum)M08.A06-
DDB_G0268270 g.p. (Dictyostelium discoideum)M08.A07-
Family M08 non-peptidase homologuesnon-peptidase homologue-
Family M08 unassigned peptidasesunassigned-