| IED ID | IndEnz0002000199 |
| Enzyme Type ID | protease000199 |
| Protein Name |
Serine protease PepD EC 3.4.21.107 HtrA-like serine protease |
| Gene Name | pepD htrA2 Rv0983 |
| Organism | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Actinobacteria Actinomycetia (high G+C Gram-positive bacteria) Corynebacteriales Mycobacteriaceae Mycobacterium Mycobacterium tuberculosis complex Mycobacterium tuberculosis Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Enzyme Sequence | MAKLARVVGLVQEEQPSDMTNHPRYSPPPQQPGTPGYAQGQQQTYSQQFDWRYPPSPPPQPTQYRQPYEALGGTRPGLIPGVIPTMTPPPGMVRQRPRAGMLAIGAVTIAVVSAGIGGAAASLVGFNRAPAGPSGGPVAASAAPSIPAANMPPGSVEQVAAKVVPSVVMLETDLGRQSEEGSGIILSAEGLILTNNHVIAAAAKPPLGSPPPKTTVTFSDGRTAPFTVVGADPTSDIAVVRVQGVSGLTPISLGSSSDLRVGQPVLAIGSPLGLEGTVTTGIVSALNRPVSTTGEAGNQNTVLDAIQTDAAINPGNSGGALVNMNAQLVGVNSAIATLGADSADAQSGSIGLGFAIPVDQAKRIADELISTGKASHASLGVQVTNDKDTLGAKIVEVVAGGAAANAGVPKGVVVTKVDDRPINSADALVAAVRSKAPGATVALTFQDPSGGSRTVQVTLGKAEQ |
| Enzyme Length | 464 |
| Uniprot Accession Number | O53896 |
| Absorption | |
| Active Site | ACT_SITE 197; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P0C0V0; ACT_SITE 236; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P0C0V0; ACT_SITE 317; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P0C0V0 |
| Activity Regulation | ACTIVITY REGULATION: Probably regulates its own activity by autocleavage, which removes the PDZ domain (PubMed:18479146). Inhibited by the serine protease inhibitor diisopropylfluorophosphate (DFP) (PubMed:20061478). Inhibited by fluoroquinolone such as ciprofloxacin, moxifloxacin and ofloxacin and their analogs (PubMed:23440996). {ECO:0000269|PubMed:18479146, ECO:0000269|PubMed:20061478, ECO:0000269|PubMed:23440996}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-|-Val.; EC=3.4.21.107; Evidence={ECO:0000269|PubMed:18479146, ECO:0000269|PubMed:20061478}; |
| DNA Binding | |
| EC Number | 3.4.21.107 |
| Enzyme Function | FUNCTION: Required for virulence (PubMed:18479146). Acts both as a protease, which degrades and/or refolds damaged substrate targets, and as a chaperone (PubMed:18479146, PubMed:20061478). Plays an important role in the stress response network mediated through the two-component regulatory system MprAB and SigE signaling networks (PubMed:20061478). May utilize its PDZ domain to recognize and process misfolded proteins at the cell membrane, leading to activation of the MprAB and SigE signaling pathways and subsequent establishment of a positive feedback loop that facilitates bacterial adaptation (PubMed:20061478). Interacts with and potentially cleaves several proteins, including the 35 kDa antigen PspA (PubMed:21445360). Proteolytic cleavage of PspA may help to maintain cell envelope homeostasis in Mycobacterium and regulate specific stress response pathways during periods of extracytoplasmic stress (PubMed:21445360). In vitro, exhibits proteolytic activity against the artificial substrate beta-casein (PubMed:18479146, PubMed:20061478). {ECO:0000269|PubMed:18479146, ECO:0000269|PubMed:20061478, ECO:0000269|PubMed:21445360}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 37 degrees Celsius. {ECO:0000269|PubMed:20061478}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is between 7.0 and 8.5. {ECO:0000269|PubMed:20061478}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (17); Chain (1); Compositional bias (1); Domain (1); Helix (7); Mutagenesis (1); Region (1); Topological domain (2); Transmembrane (1); Turn (3) |
| Keywords | 3D-structure;Cell inner membrane;Cell membrane;Cell wall;Hydrolase;Membrane;Protease;Reference proteome;Secreted;Serine protease;Stress response;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | INDUCTION: Transcribed from three distinct promoters, one that is located in the intergenic region between mprB and pepD, one that overlaps with the translational start site for mprA, and one upstream of mprA that resides in a predicted SigE-regulated promoter region. {ECO:0000269|PubMed:20061478}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:21445360}; Single-pass membrane protein {ECO:0000255}. Secreted, cell wall {ECO:0000269|PubMed:21445360}. Secreted {ECO:0000269|PubMed:21445360}. Note=Traffics from the cytoplasm through the cell membrane to the cell wall where it is autoprocessed and eventually secreted into the culture filtrate protein. {ECO:0000269|PubMed:21445360}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 1Y8T; 2Z9I; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 46,453 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |