| IED ID | IndEnz0002008035 |
| Enzyme Type ID | protease008035 |
| Protein Name |
Pro-Pro endopeptidase PPEP-1 EC 3.4.24.89 Zinc metalloprotease Zmp1 |
| Gene Name | zmp1 ppep-1 CD630_28300 |
| Organism | Clostridioides difficile (strain 630) (Peptoclostridium difficile) |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Firmicutes Clostridia Eubacteriales Peptostreptococcaceae Clostridioides Clostridioides difficile (Peptoclostridium difficile) Clostridioides difficile (strain 630) (Peptoclostridium difficile) |
| Enzyme Sequence | MRPSKKLLIAIISIFLISSVPVSAHADSTTIQQNKDTLSQIVVFPTGNYDKNEANAMVNRLANIDGKYLNALKQNNLKIKLLSGKLTDEKEYAYLKGVVPKGWEGTGKTWDDVPGLGGSTVALRIGFSNKGKGHDAINLELHETAHAIDHIVLNDISKSAQFKQIFAKEGRSLGNVNYLGVYPEEFFAESFAYYYLNQDTNSKLKSACPQTYSFLQNLAK |
| Enzyme Length | 220 |
| Uniprot Accession Number | Q183R7 |
| Absorption | |
| Active Site | ACT_SITE 143; /note="Proton acceptor"; /evidence="ECO:0000305|PubMed:24303041, ECO:0000305|PubMed:26211609" |
| Activity Regulation | ACTIVITY REGULATION: Is inhibited by the chelating agent o-phenanthroline in vitro. {ECO:0000269|PubMed:24623589}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=The enzyme catalyzes the hydrolytic cleavage of peptide bonds between two proline residues.; EC=3.4.24.89; Evidence={ECO:0000269|PubMed:24623589, ECO:0000269|PubMed:26522134}; |
| DNA Binding | |
| EC Number | 3.4.24.89 |
| Enzyme Function | FUNCTION: Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond. Exhibits a high preference for an asparagine at the P2 position and hydrophobic residues (Val, Ile, Leu) at the P3 position. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites in vivo. Has a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins such as the collagen binding protein CD630_28310, and is important for efficient infection. Is also able to cleave fibronectin and fibrinogen in vitro; cleaves at the N-terminus of the beta-chain of fibrinogen. Destabilizes the fibronectin network produced by human fibroblasts. Therefore, may be important in key steps of clostridial pathogenesis by degrading extracellular matrix components associated with the gut epithelial cells. To a lesser extent, IgA1, IgA2, and human HSP 90-beta, but not HSP 90-alpha, are also substrates for the enzyme. Is not active on different collagen types, casein and gelatin. {ECO:0000269|PubMed:24303041, ECO:0000269|PubMed:24623589, ECO:0000269|PubMed:26283789, ECO:0000269|PubMed:26522134}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Beta strand (6); Chain (1); Domain (1); Helix (12); Metal binding (3); Mutagenesis (4); Region (2); Signal peptide (1); Site (3); Turn (5) |
| Keywords | 3D-structure;Hydrolase;Metal-binding;Metalloprotease;Protease;Reference proteome;Secreted;Signal;Virulence;Zinc |
| Interact With | |
| Induction | INDUCTION: Expression is controlled by a type I c-diGMP riboswitch; elevated levels of c-diGMP repress transcription of zmp1. {ECO:0000269|PubMed:23675309}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24303041, ECO:0000269|PubMed:24623589, ECO:0000269|PubMed:26522134}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..26; /evidence=ECO:0000255 |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (22) |
| Cross Reference PDB | 2N6J; 5A0P; 5A0R; 5A0S; 5A0X; 5N12; 6R4W; 6R4X; 6R4Y; 6R4Z; 6R50; 6R51; 6R52; 6R53; 6R54; 6R55; 6R56; 6R57; 6R58; 6R59; 6R5A; 6R5B; 6R5C; |
| Mapped Pubmed ID | 26711661; 29717999; 31182482; |
| Motif | |
| Gene Encoded By | |
| Mass | 24,319 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=77 uM for synthetic FRET peptide DabcylLys-EVNPPPPD-EdansGlu {ECO:0000269|PubMed:24623589}; Vmax=0.08 nmol/sec/ug enzyme with synthetic FRET peptide DabcylLys-EVNPPPPD-EdansGlu as substrate {ECO:0000269|PubMed:24623589}; Note=kcat is 19 sec(-1) with synthetic FRET peptide DabcylLys-EVNPPPPD-EdansGlu as substrate. {ECO:0000269|PubMed:24623589}; |
| Metal Binding | METAL 142; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:26211609; METAL 146; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:26211609; METAL 185; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:26211609 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.89; |