| IED ID | IndEnz0002010717 |
| Enzyme Type ID | protease010717 |
| Protein Name |
Proteasome subunit alpha 20S proteasome alpha subunit Proteasome core protein PrcA |
| Gene Name | prcA Rv2109c |
| 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 | MSFPYFISPEQAMRERSELARKGIARAKSVVALAYAGGVLFVAENPSRSLQKISELYDRVGFAAAGKFNEFDNLRRGGIQFADTRGYAYDRRDVTGRQLANVYAQTLGTIFTEQAKPYEVELCVAEVAHYGETKRPELYRITYDGSIADEPHFVVMGGTTEPIANALKESYAENASLTDALRIAVAALRAGSADTSGGDQPTLGVASLEVAVLDANRPRRAFRRITGSALQALLVDQESPQSDGESSG |
| Enzyme Length | 248 |
| Uniprot Accession Number | P9WHU1 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: The formation of the proteasomal ATPase ARC-20S proteasome complex, likely via the docking of the C-termini of ARC into the intersubunit pockets in the alpha-rings, may trigger opening of the gate for substrate entry. Interconversion between the open-gate and close-gate conformations leads to a dynamic regulation of the 20S proteasome proteolysis activity. In vitro, chymotryptic and tryptic activities of the proteasome are both completely inhibited by epoxomicin and by the peptidyl boronate inhibitor MLN-273. Also inhibited by Mg(2+), Ca(2+) and SDS. It was also shown that certain oxathiazol-2-one compounds can act as selective suicide-substrate inhibitors of the M.tuberculosis proteasome by irreversibly cyclocarbonylating its active site threonine. Proteasome activity is potently inhibited by fellutamide B (Ki=6.8 nM), a lipopeptide aldehyde that forms a reversible bond with the beta-OH of the active site threonine (PubMed:20558127). {ECO:0000255|HAMAP-Rule:MF_00289, ECO:0000269|PubMed:16468985, ECO:0000269|PubMed:19759536, ECO:0000269|PubMed:20558127}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues (PubMed:16468985). In complex with the ATPase Mpa, degrades protein targets conjugated to a prokaryotic ubiquitin-like protein (Pup). Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins (PubMed:17082771). One function of the proteasome is to contribute to M.tuberculosis ability to resist killing by host macrophages, since the core proteasome is essential for persistence of the pathogen during the chronic phase of infection in mice (PubMed:18059281). Likely functions to recycle amino acids under nutrient starvation, thereby enabling the cell to maintain basal metabolic activities (PubMed:20711362) (By similarity). The mechanism of protection against bactericidal chemistries of the host's immune response probably involves the degradation of proteins that are irreversibly oxidized, nitrated, or nitrosated. A proteolysis-independent activity of the proteasome core is required for optimal growth of M.tuberculosis in mouse lungs and for RNI resistance; in contrast, long-term survival of M.tuberculosis in stationary phase and during starvation in vitro and in the chronic phase of mouse infection required a proteolytically active proteasome (PubMed:20711362). {ECO:0000250|UniProtKB:A0QZ46, ECO:0000255|HAMAP-Rule:MF_00289, ECO:0000269|PubMed:16468985, ECO:0000269|PubMed:17082771, ECO:0000269|PubMed:18059281, ECO:0000269|PubMed:20711362}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Protein degradation; proteasomal Pup-dependent pathway. {ECO:0000255|HAMAP-Rule:MF_00289}. |
| nucleotide Binding | |
| Features | Beta strand (13); Chain (1); Helix (9); Initiator methionine (1); Modified residue (4); Mutagenesis (1) |
| Keywords | 3D-structure;Acetylation;Cytoplasm;Direct protein sequencing;Phosphoprotein;Proteasome;Reference proteome;Virulence |
| Interact With | P9WHT9 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00289}. |
| Modified Residue | MOD_RES 2; /note="N-acetylserine; partial"; /evidence="ECO:0000269|PubMed:17259624, ECO:0007744|PubMed:21969609"; MOD_RES 84; /note="Phosphothreonine"; /evidence="ECO:0000269|PubMed:25224505"; MOD_RES 178; /note="Phosphothreonine"; /evidence="ECO:0000269|PubMed:25224505"; MOD_RES 202; /note="Phosphothreonine"; /evidence="ECO:0000269|PubMed:25224505" |
| Post Translational Modification | PTM: Phosphorylated by the PknB kinase at three threonine residues (Thr-84, Thr-202, and Thr-178) in a sequential manner. Phosphorylation enhances proteolytic activity of the proteasome. {ECO:0000269|PubMed:25224505}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (3); X-ray crystallography (20) |
| Cross Reference PDB | 2FHG; 2FHH; 3H6F; 3H6I; 3HF9; 3HFA; 3KRD; 3MFE; 3MI0; 3MKA; 5LZP; 5THO; 5TRG; 5TRR; 5TRS; 5TRY; 5TS0; 6BGL; 6BGO; 6OCW; 6OCZ; 6ODE; 6WNK; |
| Mapped Pubmed ID | 27839949; 27976853; 29414791; 31560200; 33949190; |
| Motif | |
| Gene Encoded By | |
| Mass | 26,881 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=56 uM for succinyl-LLVY-7-amino-4-methylcoumarin {ECO:0000269|PubMed:16468985}; Vmax=0.24 nmol/min/mg enzyme with succinyl-LLVY-7-amino-4-methylcoumarin as substrate {ECO:0000269|PubMed:16468985}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |