title: The proteasome from Thermoplasma acidophilum is neither a cysteine nor a serine protease.
abstract: The 20 S proteasome, found in eukaryotes and in the archaebacterium Thermoplasma acidophilum, forms the proteolytic core of the 26 S proteasome which is the central protease of the non-lysosomal protein degradation pathway. Inhibitor studies have indicated that the 20 S proteasome may be an unusual type of cysteine or serine protease and a recent study of the Thermoplasma beta subunit has indicated that it carries the proteolytic activity. We have attempted to obtain information on the nature of the active site by mutating the only cysteine, both histidines and two completely conserved aspartates in the archaebacterial complex as well as all serines of the beta subunit, without decreasing the catalytic activity of the enzyme to any significant extent. Indeed, mutation of the conserved aspartate in the beta subunit increased the activity of the proteasome threefold. We conclude that the proteasome is not a cysteine or serine protease.
authors.affiliation: Max-Planck-Institut für Biochemie, Martinsried, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Seemüller
authors.forename: A
authors.initials: A
authors.lastname: Lupas
authors.forename: F
authors.initials: F
authors.lastname: Zühl
authors.forename: P
authors.initials: P
authors.lastname: Zwickl
authors.forename: W
authors.initials: W
authors.lastname: Baumeister
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D002461:Cell Line, Transformed; D003545:Cysteine / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D046988:Proteasome Endopeptidase Complex; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013822:Thermoplasma / Q000201:enzymology* / Q000235:genetics
chemical_list: D009097:Multienzyme Complexes; D001224:Aspartic Acid; D006639:Histidine; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D003545:Cysteine