Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.25.1 extracted from

  • Deriziotis, P.; Andre, R.; Smith, D.M.; Goold, R.; Kinghorn, K.J.; Kristiansen, M.; Nathan, J.A.; Rosenzweig, R.; Krutauz, D.; Glickman, M.H.; Collinge, J.; Goldberg, A.L.; Tabrizi, S.J.
    Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry (2011), EMBO J., 30, 3065-3077.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.25.1

Activating Compound

Activating Compound Comment Organism Structure
Rpt2 the 19S ATPase subunits, Rpt2 and Rpt5, bind ATP, their C-termini dock into intersubunit pockets in the 20S particle alpha-ring and induce gate opening, activating the protease activity. A conserved HbYX motif in the C-terminus is required Homo sapiens
Rpt5 the 19S ATPase subunits, Rpt2 and Rpt5, bind ATP, their C-termini dock into intersubunit pockets in the 20S particle alpha-ring and induce gate opening, activating the protease activity. A conserved HbYX motif in the C-terminus is required Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information construction of open-gated mutant, alpha3DELTAN 20S particles, that show much higher basal chymotrypsin-like activity compared with wild-type 20S activity, and are not inhibitable by prion protein isoforms, overview Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
epoxomicin EPOX, a specific proteasome inhibitor, abolishes chymotrypsin-like activity in both wild-type 20S and a3DN 20S mutant proteasomes after pre-treatment with 50 mM epoxomicin Homo sapiens
prion protein recombinant mouse aggregated beta-PrP binds directly to human 20S and 26S proteasomes, i.e. its 20S core particle, overview. Conversion of cellular prion protein, PrPC, to toxic beta-sheet isoforms, PrPSc, which inhibit the ubiquitin-proteasome system and lead to accumulation of the system substrates, are associated with the prion diseases. PrP aggregates inhibit by stabilising the closed conformation of the substrate entry channel. The 20S proteasome is not inhibited when the gate in the alpha-ring is open due to a truncation mutation or by association with PA26/PA28. Modelling of location of aggregated beta-sheet rich PrP binding to the 20S proteasome and inhibition mechanism, detailed overview Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Boc-Leu-Arg-Arg-7-amido-4-methylcoumarin + H2O trypsin-like activity Homo sapiens Boc-Leu-Arg-Arg + 7-amino-4-methylcoumarin
-
 ?
casein + H2O
-
 Homo sapiens ?
-
 ?