Family M91
Summary for family M91
| Family type peptidase | M91.001 - NleD peptidase (Escherichia coli-type) (Escherichia coli), MEROPS Accession MER0331730 (peptidase unit: 1-232) |
| Content of family | Family M91 contains endopeptidases. |
| History |
Identifier created: MEROPS 9.7 (1 August 2012)
NleD protein (M91.001) from enteropathogenic strains of Escherichia coli is a virulence factor that helps inactivate the inflammatory response by cleavage of host mitogen-activated protein kinase 9 (Baruch et al., 2011). |
| Catalytic type | Metallo |
| Active site residues | H142 E143 H146 |
| Active site | NleD is assumed to be a zinc metallopeptidase because of the presence of an HEXXH motif, characteristic of peptidases in clan MA. Mutagenesis studies have confirmed that the glutamic acid within this motif is essential for activity (Baruch et al., 2011), and it is assumed to be a catalytic residue. The histidines in the HEXXH motif are assumed to be metal ligands, but the third metal ligand is unknown. |
| Inhibitors | The metal chelator 1,10-phenanthroline is inhibitory (Baruch et al., 2011). |
| Molecular structure | No tertiary structure has been solved for any member of the family. The family is included in clan MA because of the presence of the zinc-binding motif, HEXXH, and because NleD is not a membrane protein. |
| Clan | MA |
| Subclan | MA(E) |
|
Distribution of family
|
Bacteria |
details |
|
|
|
Archaea |
- |
|
|
|
Protozoa |
- |
|
|
|
Fungi |
- |
|
|
|
Plants |
- |
|
|
|
Animals |
- |
|
|
|
Viruses |
- |
|
| Biological functions | Pathogenetic E. coli injects virulence factors into host cells using the type III secretion system. Both NleC (M85.001) and NleD are secreted in this way and both target the inflammatory response of the host by interfering with the NF-kappaB and c-Jun N-terminal kinase (JNK) pathways. By cleaving and inactivating RelA and JNK, NleC and NleD block NF-kappaB and AP-1 activation. NleD cleaves JNK within its activation loop, separating the two essential phosphorylation sites (Baruch et al., 2011). |
| Statistics for family M91 | Sequences: | 10 |
| Identifiers: | 1 |
| Identifiers with PDB entries: | 0 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
