The Ntn hydrolases (N-terminal nucleophile) are a diverse superfamily of of enzymes that are activated autocatalytically via an N-terminally lcated nucleophilic amino acid. N-terminal nucleophile (NTN-) hydrolase superfamily, which contains a four-layered alpha, beta, beta, alpha core structure. This family of hydrolases includes penicillin acylase, the 20S proteasome alpha and beta subunits, and glutamate synthase. The mechanism of activation of these proteins is conserved, although they differ in their substrate specificities. All known members catalyze the hydrolysis of amide bonds in either proteins or small molecules, and each one of them is synthesized as a preprotein. For each, an autocatalytic endoproteolytic process generates a new N-terminal residue. This mature N-terminal residue is central to catalysis and acts as both a polarizing base and a nucleophile during the reaction. The N-terminal amino group acts as the proton acceptor and activates either the nucleophilic hydroxyl in a Ser or Thr residue or the nucleophilic thiol in a Cys residue. The position of the N-terminal nucleophile in the active site and the mechanism of catalysis are conserved in this family, despite considerable variation in the protein sequences.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1951422265   1 MLVRQPVSVGGSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEGVERRV 70
Cdd:cd03762   119 MLIRQPFAIGGSGSTYIYGYVDANYKPGMTLEECIKFVKNALSLAMSRDGSSGGVIRLVIITKDGVERKF 188

proteasome beta type-6 subunit. The 20S proteasome, multisubunit proteolytic complex, is the central enzyme of nonlysosomal protein degradation in both the cytosol and nucleus. It is composed of 28 subunits arranged as four homoheptameric rings that stack on top of one another forming an elongated alpha-beta-beta-alpha cylinder with a central cavity. The proteasome alpha and beta subunits are members of the N-terminal nucleophile (Ntn)-hydrolase superfamily. Their N-terminal threonine residues are exposed as a nucleophile in peptide bond hydrolysis. Mammals have 7 alpha and 7 beta proteasome subunits while archaea have one of each.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1951422265   1 MLVRQPVSVGGSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEGVERRV 70
Cdd:cd03762   119 MLIRQPFAIGGSGSTYIYGYVDANYKPGMTLEECIKFVKNALSLAMSRDGSSGGVIRLVIITKDGVERKF 188

Proteasome subunit; The proteasome is a multisubunit structure that degrades proteins. Protein degradation is an essential component of regulation because proteins can become misfolded, damaged, or unnecessary. Proteasomes and their homologs vary greatly in complexity: from HslV (heat shock locus v), which is encoded by 1 gene in bacteria, to the eukaryotic 20S proteasome, which is encoded by more than 14 genes. Recently evidence of two novel groups of bacterial proteasomes was proposed. The first is Anbu, which is sparsely distributed among cyanobacteria and proteobacteria. The second is call beta-proteobacteria proteasome homolog (BPH).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1951422265  11 GSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASI 61
Cdd:pfam00227 138 GSGSQYAYGVLEKLYRPDLTLEEAVELAVKALKEAIDRDALSGGNIEVAVI 188

Proteasome subunit beta type-5; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1951422265  11 GSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEG 65
Cdd:PTZ00488  168 GSGSTYAYGVLDAGFKWDLNDEEAQDLGRRAIYHATFRDAYSGGAINLYHMQKDG 222

proteasome beta type-6 subunit. The 20S proteasome, multisubunit proteolytic complex, is the central enzyme of nonlysosomal protein degradation in both the cytosol and nucleus. It is composed of 28 subunits arranged as four homoheptameric rings that stack on top of one another forming an elongated alpha-beta-beta-alpha cylinder with a central cavity. The proteasome alpha and beta subunits are members of the N-terminal nucleophile (Ntn)-hydrolase superfamily. Their N-terminal threonine residues are exposed as a nucleophile in peptide bond hydrolysis. Mammals have 7 alpha and 7 beta proteasome subunits while archaea have one of each.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1951422265   1 MLVRQPVSVGGSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEGVERRV 70
Cdd:cd03762   119 MLIRQPFAIGGSGSTYIYGYVDANYKPGMTLEECIKFVKNALSLAMSRDGSSGGVIRLVIITKDGVERKF 188

20S proteasome, alpha and beta subunits [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1951422265  11 GSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEGVER 68
Cdd:COG0638   167 GSGSPFARGVLEKEYREDLSLDEAVELALRALYSAAERDSASGDGIDVAVITEDGFRE 224

proteasome_protease_HslV. This group contains the eukaryotic proteosome alpha and beta subunits and the prokaryotic protease hslV subunit. Proteasomes are large multimeric self-compartmentalizing proteases, involved in the clearance of misfolded proteins, the breakdown of regulatory proteins, and the processing of proteins such as the preparation of peptides for immune presentation. Two main proteasomal types are distinguished by their different tertiary structures: the eukaryotic/archeal 20S proteasome and the prokaryotic proteasome-like heat shock protein encoded by heat shock locus V, hslV. The proteasome core particle is a highly conserved cylindrical structure made up of non-identical subunits that have their active sites on the inner walls of a large central cavity. The proteasome subunits of bacteria, archaea, and eukaryotes all share a conserved Ntn (N terminal nucleophile) hydrolase fold and a catalytic mechanism involving an N-terminal nucleophilic threonine that is exposed by post-translational processing of an inactive propeptide.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1951422265   1 MLVRQPVSVGGSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASI 61
Cdd:cd01906   122 SYIEYKATAIGSGSQYALGILEKLYKPDMTLEEAIELALKALKSALERDLYSGGNIEVAVI 182

proteasome endopeptidase complex, archaeal, beta subunit; This protein family describes the archaeal proteasome beta subunit, homologous to both the alpha subunit and to the alpha and beta subunits of eukaryotic proteasome subunits. This family is universal in the first 29 complete archaeal genomes but occasionally is duplicated. [Protein fate, Degradation of proteins, peptides, and glycopeptides]

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1951422265  11 GSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEGV 66
Cdd:TIGR03634 130 GSGSPVAYGVLEDEYREDMSVEEAKKLAVRAIKSAIERDVASGNGIDVAVITKDGV 185

Proteasome subunit beta type-5; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1951422265  11 GSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEG 65
Cdd:PTZ00488  168 GSGSTYAYGVLDAGFKWDLNDEEAQDLGRRAIYHATFRDAYSGGAINLYHMQKDG 222

proteasome beta type-7 subunit. The 20S proteasome, multisubunit proteolytic complex, is the central enzyme of nonlysosomal protein degradation in both the cytosol and nucleus. It is composed of 28 subunits arranged as four homoheptameric rings that stack on top of one another forming an elongated alpha-beta-beta-alpha cylinder with a central cavity. The proteasome alpha and beta subunits are members of the N-terminal nucleophile (Ntn)-hydrolase superfamily. Their N-terminal threonine residues are exposed as a nucleophile in peptide bond hydrolysis. Mammals have 7 alpha and 7 beta proteasome subunits while archaea have one of each.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1951422265  11 GSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGVVRLASISEEGVE 67
Cdd:cd03763   128 GSGSLAAMSVLEDRYKPDMTEEEAKKLVCEAIEAGIFNDLGSGSNVDLCVITKDGVE 184

The Ntn hydrolases (N-terminal nucleophile) are a diverse superfamily of of enzymes that are activated autocatalytically via an N-terminally lcated nucleophilic amino acid. N-terminal nucleophile (NTN-) hydrolase superfamily, which contains a four-layered alpha, beta, beta, alpha core structure. This family of hydrolases includes penicillin acylase, the 20S proteasome alpha and beta subunits, and glutamate synthase. The mechanism of activation of these proteins is conserved, although they differ in their substrate specificities. All known members catalyze the hydrolysis of amide bonds in either proteins or small molecules, and each one of them is synthesized as a preprotein. For each, an autocatalytic endoproteolytic process generates a new N-terminal residue. This mature N-terminal residue is central to catalysis and acts as both a polarizing base and a nucleophile during the reaction. The N-terminal amino group acts as the proton acceptor and activates either the nucleophilic hydroxyl in a Ser or Thr residue or the nucleophilic thiol in a Cys residue. The position of the N-terminal nucleophile in the active site and the mechanism of catalysis are conserved in this family, despite considerable variation in the protein sequences.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1951422265   9 VGGSGSTYIYGFMDSNYKPGLSKDQCLELTAAALS 43
Cdd:cd01901   129 ATGSRSQRAKSLLEKLYKPDMTLEEAVELALKALK 163

archaeal proteasome endopeptidase complex subunit alpha;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1951422265  11 GSGSTYIYGFMDSNYKPGLSKDQCLELTAAALSLAMERDGSSGGvVRLASISEE 64
Cdd:PRK03996  168 GAGRDTVMEFLEKNYKEDLSLEEAIELALKALAKANEGKLDPEN-VEIAYIDVE 220