Family M8
Summary for family M8
| Name | Peptidase family M8 (leishmanolysin family) |
|---|
| Family type peptidase | M08.001 - leishmanolysin (Leishmania major), MEROPS Accession MER0001165 (peptidase unit: 101-602) |
| Content of family | Peptidase family M8 contains the metallo-endopeptidase leishmanolysin and its homologues. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
|
| Catalytic type | Metallo |
| Active site residues | H264 E265 H268 H334 M345 |
| Active site | Leishmanolysin 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 specificities | Leishmanolysin 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. |
| Inhibitors | Leishmanolysin 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 structure | The 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). |
| Clan | MA |
| Subclan | MA(M) |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of thermolysin, the type example for clan MA. |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| leishmanolysin | M08.001 | Yes |
| invadolysin (invertebrate-type) | M08.002 | - |
| leishmanolysin-2 | M08.003 | - |
| leishmanolysin-3 | M08.004 | - |
| 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 homologues | non-peptidase homologue | - |
| Family M08 unassigned peptidases | unassigned | - |
