EzCatDB: M00351
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DB codeM00351
RLCP classification1.13.30020.28 : Hydrolysis
CATH domainDomain 12.120.10.60 : Neuraminidase
Domain 22.130.10.10 : Methylamine Dehydrogenase; Chain H
Domain 33.30.750.44 : Transcription Regulator spoIIAACatalytic domain
Domain 42.30.42.10 : Pdz3 Domain
Domain 53.90.226.10 : 2-enoyl-CoA Hydratase; Chain A, domain 1Catalytic domain
E.C.3.4.21.-,3.4.25.1
CSA1k32


Enzyme Name
UniProtKBKEGG

P96086
Protein nameTricorn proteaseProteasome endopeptidase complex
Ingensin
Macropain
Multicatalytic endopeptidase complex
Prosome
Multicatalytic proteinase (complex)
MCP
Proteasome
Large multicatalytic protease
Multicatalytic proteinase
Proteasome organelle
Alkaline protease
26S protease
Tricorn proteinase
Tricorn protease
SynonymsEC 3.4.21.-
RefSeqNP_394941.1 (Protein)
NC_002578.1 (DNA/RNA sequence)
MEROPSS41.005 (Serine)
PfamPF07676 (PD40)
PF03572 (Peptidase_S41)
[Graphical view]


UniProtKB:Accession NumberP96086
Entry nameTRI_THEAC
Activity
SubunitPart of the Tricorn proteolytic complex. Assembles to form a hexameric toroid, 20 copies of which may then assemble to form an icosahedral supermolecule of 14.6 MDa.
Subcellular locationCytoplasm.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00012C00012I00087I00085I00086
CompoundPeptidePeptidePeptidyl-Ser-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typepeptide/proteinpeptide/protein


ChEBI




PubChem




             
1k32A01UnboundUnboundUnboundUnboundUnbound
1k32B01UnboundUnboundUnboundUnboundUnbound
1k32C01UnboundUnboundUnboundUnboundUnbound
1k32D01UnboundUnboundUnboundUnboundUnbound
1k32E01UnboundUnboundUnboundUnboundUnbound
1k32F01UnboundUnboundUnboundUnboundUnbound
1n6dA01UnboundUnboundUnboundUnboundUnbound
1n6dB01UnboundUnboundUnboundUnboundUnbound
1n6dC01UnboundUnboundUnboundUnboundUnbound
1n6dD01UnboundUnboundUnboundUnboundUnbound
1n6dE01UnboundUnboundUnboundUnboundUnbound
1n6dF01UnboundUnboundUnboundUnboundUnbound
1n6eA01UnboundUnboundUnboundUnboundUnbound
1n6eC01UnboundUnboundUnboundUnboundUnbound
1n6eE01UnboundUnboundUnboundUnboundUnbound
1n6eG01UnboundUnboundUnboundUnboundUnbound
1n6eI01UnboundUnboundUnboundUnboundUnbound
1n6eK01UnboundUnboundUnboundUnboundUnbound
1n6fA01UnboundUnboundUnboundUnboundUnbound
1n6fB01UnboundUnboundUnboundUnboundUnbound
1n6fC01UnboundUnboundUnboundUnboundUnbound
1n6fD01UnboundUnboundUnboundUnboundUnbound
1n6fE01UnboundUnboundUnboundUnboundUnbound
1n6fF01UnboundUnboundUnboundUnboundUnbound
1k32A02UnboundUnboundUnboundUnboundUnbound
1k32B02UnboundUnboundUnboundUnboundUnbound
1k32C02UnboundUnboundUnboundUnboundUnbound
1k32D02UnboundUnboundUnboundUnboundUnbound
1k32E02UnboundUnboundUnboundUnboundUnbound
1k32F02UnboundUnboundUnboundUnboundUnbound
1n6dA02UnboundUnboundUnboundUnboundUnbound
1n6dB02UnboundUnboundUnboundUnboundUnbound
1n6dC02UnboundUnboundUnboundUnboundUnbound
1n6dD02UnboundUnboundUnboundUnboundUnbound
1n6dE02UnboundUnboundUnboundUnboundUnbound
1n6dF02UnboundUnboundUnboundUnboundUnbound
1n6eA02UnboundUnboundUnboundUnboundUnbound
1n6eC02UnboundUnboundUnboundUnboundUnbound
1n6eE02UnboundUnboundUnboundUnboundUnbound
1n6eG02UnboundUnboundUnboundUnboundUnbound
1n6eI02UnboundUnboundUnboundUnboundUnbound
1n6eK02UnboundUnboundUnboundUnboundUnbound
1n6fA02UnboundUnboundUnboundUnboundUnbound
1n6fB02UnboundUnboundUnboundUnboundUnbound
1n6fC02UnboundUnboundUnboundUnboundUnbound
1n6fD02UnboundUnboundUnboundUnboundUnbound
1n6fE02UnboundUnboundUnboundUnboundUnbound
1n6fF02UnboundUnboundUnboundUnboundUnbound
1k32A03UnboundUnboundUnboundUnboundUnbound
1k32B03UnboundUnboundUnboundUnboundUnbound
1k32C03UnboundUnboundUnboundUnboundUnbound
1k32D03UnboundUnboundUnboundUnboundUnbound
1k32E03UnboundUnboundUnboundUnboundUnbound
1k32F03UnboundUnboundUnboundUnboundUnbound
1n6dA03UnboundUnboundUnboundUnboundUnbound
1n6dB03UnboundUnboundUnboundUnboundUnbound
1n6dC03UnboundUnboundUnboundUnboundUnbound
1n6dD03UnboundUnboundUnboundUnboundUnbound
1n6dE03UnboundUnboundUnboundUnboundUnbound
1n6dF03UnboundUnboundUnboundUnboundUnbound
1n6eA03UnboundUnboundUnboundUnboundUnbound
1n6eC03UnboundUnboundUnboundUnboundUnbound
1n6eE03UnboundUnboundUnboundUnboundUnbound
1n6eG03UnboundUnboundUnboundUnboundUnbound
1n6eI03UnboundUnboundUnboundUnboundUnbound
1n6eK03UnboundUnboundUnboundUnboundUnbound
1n6fA03UnboundUnboundUnboundUnboundUnbound
1n6fB03UnboundUnboundUnboundUnboundUnbound
1n6fC03UnboundUnboundUnboundUnboundUnbound
1n6fD03UnboundUnboundUnboundUnboundUnbound
1n6fE03UnboundUnboundUnboundUnboundUnbound
1n6fF03UnboundUnboundUnboundUnboundUnbound
1k32A04UnboundUnboundUnboundUnboundUnbound
1k32B04UnboundUnboundUnboundUnboundUnbound
1k32C04UnboundUnboundUnboundUnboundUnbound
1k32D04UnboundUnboundUnboundUnboundUnbound
1k32E04UnboundUnboundUnboundUnboundUnbound
1k32F04UnboundUnboundUnboundUnboundUnbound
1n6dA04UnboundUnboundUnboundUnboundUnbound
1n6dB04UnboundUnboundUnboundUnboundUnbound
1n6dC04UnboundUnboundUnboundUnboundUnbound
1n6dD04UnboundUnboundUnboundUnboundUnbound
1n6dE04UnboundUnboundUnboundUnboundUnbound
1n6dF04UnboundUnboundUnboundUnboundUnbound
1n6eA04UnboundUnboundUnboundUnboundUnbound
1n6eC04UnboundUnboundUnboundUnboundUnbound
1n6eE04UnboundUnboundUnboundUnboundUnbound
1n6eG04UnboundUnboundUnboundUnboundUnbound
1n6eI04UnboundUnboundUnboundUnboundUnbound
1n6eK04UnboundUnboundUnboundUnboundUnbound
1n6fA04UnboundUnboundUnboundUnboundUnbound
1n6fB04UnboundUnboundUnboundUnboundUnbound
1n6fC04UnboundUnboundUnboundUnboundUnbound
1n6fD04UnboundUnboundUnboundUnboundUnbound
1n6fE04UnboundUnboundUnboundUnboundUnbound
1n6fF04UnboundUnboundUnboundUnboundUnbound
1k32A05UnboundUnboundUnboundUnboundUnbound
1k32B05UnboundUnboundUnboundUnboundUnbound
1k32C05UnboundUnboundUnboundUnboundUnbound
1k32D05UnboundUnboundUnboundUnboundUnbound
1k32E05UnboundUnboundUnboundUnboundUnbound
1k32F05UnboundUnboundUnboundUnboundUnbound
1n6dA05UnboundUnboundUnboundIntermediate-analogue:ARG-VAL-ARG-LYS(chain G)Unbound
1n6dB05UnboundUnboundUnboundIntermediate-analogue:ARG-VAL-ARG-LYS(chain H)Unbound
1n6dC05UnboundUnboundUnboundIntermediate-analogue:ARG-VAL-ARG-LYS(chain I)Unbound
1n6dD05UnboundUnboundUnboundIntermediate-analogue:ARG-VAL-ARG-LYS(chain J)Unbound
1n6dE05UnboundUnboundUnboundIntermediate-analogue:ARG-VAL-ARG-LYS(chain K)Unbound
1n6dF05UnboundUnboundUnboundIntermediate-analogue:ARG-VAL-ARG-LYS(chain L)Unbound
1n6eA05UnboundUnboundUnboundUnboundTransition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE(chain B)
1n6eC05UnboundUnboundUnboundUnboundTransition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE(chain D)
1n6eE05UnboundUnboundUnboundUnboundTransition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE(chain F)
1n6eG05UnboundUnboundUnboundUnboundTransition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE(chain H)
1n6eI05UnboundUnboundUnboundUnboundTransition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE(chain J)
1n6eK05UnboundUnboundUnboundUnboundTransition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE(chain L)
1n6fA05UnboundUnboundTransition-state-analogue:DKTUnboundUnbound
1n6fB05UnboundUnboundTransition-state-analogue:DKTUnboundUnbound
1n6fC05UnboundUnboundTransition-state-analogue:DKTUnboundUnbound
1n6fD05UnboundUnboundTransition-state-analogue:DKTUnboundUnbound
1n6fE05UnboundUnboundTransition-state-analogue:DKTUnboundUnbound
1n6fF05UnboundUnboundTransition-state-analogue:DKTUnboundUnbound

Active-site residues
resource
literature [7],[8],[9]
pdbCatalytic residuesMain-chain involved in catalysis
          
1k32A01       
 
1k32B01       
 
1k32C01       
 
1k32D01       
 
1k32E01       
 
1k32F01       
 
1n6dA01       
 
1n6dB01       
 
1n6dC01       
 
1n6dD01       
 
1n6dE01       
 
1n6dF01       
 
1n6eA01       
 
1n6eC01       
 
1n6eE01       
 
1n6eG01       
 
1n6eI01       
 
1n6eK01       
 
1n6fA01       
 
1n6fB01       
 
1n6fC01       
 
1n6fD01       
 
1n6fE01       
 
1n6fF01       
 
1k32A02       
 
1k32B02       
 
1k32C02       
 
1k32D02       
 
1k32E02       
 
1k32F02       
 
1n6dA02       
 
1n6dB02       
 
1n6dC02       
 
1n6dD02       
 
1n6dE02       
 
1n6dF02       
 
1n6eA02       
 
1n6eC02       
 
1n6eE02       
 
1n6eG02       
 
1n6eI02       
 
1n6eK02       
 
1n6fA02       
 
1n6fB02       
 
1n6fC02       
 
1n6fD02       
 
1n6fE02       
 
1n6fF02       
 
1k32A03SER 745;HIS 746
 
1k32B03SER 745;HIS 746
 
1k32C03SER 745;HIS 746
 
1k32D03SER 745;HIS 746
 
1k32E03SER 745;HIS 746
 
1k32F03SER 745;HIS 746
 
1n6dA03SER 745;HIS 746
 
1n6dB03SER 745;HIS 746
 
1n6dC03SER 745;HIS 746
 
1n6dD03SER 745;HIS 746
 
1n6dE03SER 745;HIS 746
 
1n6dF03SER 745;HIS 746
 
1n6eA03SER 745;HIS 746
 
1n6eC03SER 745;HIS 746
 
1n6eE03SER 745;HIS 746
 
1n6eG03SER 745;HIS 746
 
1n6eI03SER 745;HIS 746
 
1n6eK03SER 745;HIS 746
 
1n6fA03SER 745;HIS 746
 
1n6fB03SER 745;HIS 746
 
1n6fC03SER 745;HIS 746
 
1n6fD03SER 745;HIS 746
 
1n6fE03SER 745;HIS 746
 
1n6fF03SER 745;HIS 746
 
1k32A04       
 
1k32B04       
 
1k32C04       
 
1k32D04       
 
1k32E04       
 
1k32F04       
 
1n6dA04       
 
1n6dB04       
 
1n6dC04       
 
1n6dD04       
 
1n6dE04       
 
1n6dF04       
 
1n6eA04       
 
1n6eC04       
 
1n6eE04       
 
1n6eG04       
 
1n6eI04       
 
1n6eK04       
 
1n6fA04       
 
1n6fB04       
 
1n6fC04       
 
1n6fD04       
 
1n6fE04       
 
1n6fF04       
 
1k32A05SER 965;GLU 1023
GLY 918;ASP 966
1k32B05SER 965;GLU 1023
GLY 918;ASP 966
1k32C05SER 965;GLU 1023
GLY 918;ASP 966
1k32D05SER 965;GLU 1023
GLY 918;ASP 966
1k32E05SER 965;GLU 1023
GLY 918;ASP 966
1k32F05SER 965;GLU 1023
GLY 918;ASP 966
1n6dA05SER 965;GLU 1023
GLY 918;ASP 966
1n6dB05SER 965;GLU 1023
GLY 918;ASP 966
1n6dC05SER 965;GLU 1023
GLY 918;ASP 966
1n6dD05SER 965;GLU 1023
GLY 918;ASP 966
1n6dE05SER 965;GLU 1023
GLY 918;ASP 966
1n6dF05SER 965;GLU 1023
GLY 918;ASP 966
1n6eA05SER 965;GLU 1023
GLY 918;ASP 966
1n6eC05SER 965;GLU 1023
GLY 918;ASP 966
1n6eE05SER 965;GLU 1023
GLY 918;ASP 966
1n6eG05SER 965;GLU 1023
GLY 918;ASP 966
1n6eI05SER 965;GLU 1023
GLY 918;ASP 966
1n6eK05SER 965;GLU 1023
GLY 918;ASP 966
1n6fA05SER 965;GLU 1023
GLY 918;ASP 966
1n6fB05SER 965;GLU 1023
GLY 918;ASP 966
1n6fC05SER 965;GLU 1023
GLY 918;ASP 966
1n6fD05SER 965;GLU 1023
GLY 918;ASP 966
1n6fE05SER 965;GLU 1023
GLY 918;ASP 966
1n6fF05SER 965;GLU 1023
GLY 918;ASP 966

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]p.467
[8]p.1159-1161
[9]p.1047

references
[1]
PubMed ID8910281
JournalScience
Year1996
Volume274
Pages1385-9
AuthorsTamura T, Tamura N, Cejka Z, Hegerl R, Lottspeich F, Baumeister W
TitleTricorn protease--the core of a modular proteolytic system.
[2]
CommentsTHREE-DIMENSIONAL RECONSTRUCTION FROM ELECTRON MICROGRAPHS.
PubMed ID9659903
JournalMol Cell
Year1997
Volume1
Pages59-65
AuthorsWalz J, Tamura T, Tamura N, Grimm R, Baumeister W, Koster AJ
TitleTricorn protease exists as an icosahedral supermolecule in vivo.
[3]
CommentsCHARACTERIZATION OF PROTEIN INTERACTION.
PubMed ID9845366
JournalCell
Year1998
Volume95
Pages637-48
AuthorsTamura N, Lottspeich F, Baumeister W, Tamura T
TitleThe role of tricorn protease and its aminopeptidase-interacting factors in cellular protein degradation.
[4]
CommentsDOMAINS.
PubMed ID10518749
JournalFEMS Microbiol Lett
Year1999
Volume179
Pages447-51
AuthorsPonting CP, Pallen MJ
Titlebeta-propeller repeats and a PDZ domain in the tricorn protease: predicted self-compartmentalisation and C-terminal polypeptide-binding strategies of substrate selection.
[5]
CommentsTHREE-DIMENSIONAL RECONSTRUCTION (1.3 NM) BY ELECTRON CRYOMICROSCOPY.
PubMed ID10600560
JournalJ Struct Biol
Year1999
Volume128
Pages65-8
AuthorsWalz J, Koster AJ, Tamura T, Baumeister W
TitleCapsids of tricorn protease studied by electron cryomicroscopy.
[6]
CommentsCRYSTALLIZATION.
PubMed ID11469880
JournalJ Struct Biol
Year2001
Volume134
Pages83-7
AuthorsBosch J, Tamura T, Bourenkov G, Baumeister W, Essen LO
TitlePurification, crystallization, and preliminary X-ray diffraction analysis of the Tricorn protease hexamer from Thermoplasma acidophilum.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), MUTAGENESIS OF 131-ARG-ARG-132; HIS-746 AND SER-965.
PubMed ID11719810
JournalNature
Year2001
Volume414
Pages466-70
AuthorsBrandstetter H, Kim JS, Groll M, Huber R
TitleCrystal structure of the tricorn protease reveals a protein disassembly line.
Related PDB1k32
[8]
PubMed ID12437101
JournalBiol Chem
Year2002
Volume383
Pages1157-65
AuthorsBrandstetter H, Kim JS, Groll M, Gottig P, Huber R
TitleStructural basis for the processive protein degradation by tricorn protease.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
PubMed ID12470958
JournalJ Mol Biol
Year2002
Volume324
Pages1041-50
AuthorsKim JS, Groll M, Musiol HJ, Behrendt R, Kaiser M, Moroder L, Huber R, Brandstetter H
TitleNavigation inside a protease: substrate selection and product exit in the tricorn protease from Thermoplasma acidophilum.
Related PDB1n6d,1n6e,1n6f

comments
This enzyme belongs to peptidase family-41B.
The 120kD monomers of this protease assemble to form a hexameric complex, which could assemble further into an icosahedral capsid (see [1], [2], [5]). Each hexamer is a trimer of dimers, which forms a toroid structure (see [7]). The capsid structure is designed to avoid the destruction of proteins not destined for degradation, like proteasome (M00123 and M00174 in EzCatDB) (see [1], [2]).
This enzyme cooperates with three additional proteases, interacting factors, F1, F2 and F3 (see [3], [7]). F2 and F3 are homologous to each other ([3]). In Thermoplasma (archea) cells, proteins may be degraded in a pathway where this enzyme degrades proteins into free amino acids along with proteasome and the interacting factors (see [3]). Firstly, the proteasome degrades proteins processively, generating a pool of oligopeptides, which have a size of 6 to 12 residues. In the next stage, this enzyme efficiently cleaves the oligopeptides, yielding peptides that are mostly 2 to 4 residues in size. Finally, the three interacting factors cleave the short peptides that are 2 to 4 residues, producing free amino acids. F1 is involved in the release of proline residues, as proline iminopeptidase (homologous to S00353 in EzCatDB)(see [3]). F2 is for the release of basic amino acids, whereas F3 is for the release of acidic residues (see [3]).
Each subunit is divided into five domains: six-bladed beta-propeller (beta6), seven-bladed beta-propeller (beta7), helical bundle (C1), PDZ-like domain and alpha-beta sandwich (C2)(see [7], [8]).
The PDZ-like domain seems to be involved in recognition of the C-terminal region of substrate peptides (see [4], [8]). The two beta-propeller domains exclude large folded substrates from its sequestered active site, by acting as a filtering device (see [4], [8], [9]).
C1 and C2 are core domains that have active site (see [7], [8]). The nucleophilic residue, Ser965, on the C2 domain and general base, His746, on the C1 domain are particularly crucial in trypsin-like reaction mechanism ([7], [8]). The mainchain amide group of Asp966 and Gly918 form an oxyanion hole, which stabilizes the tetrahedral transition-state and acyl-enzyme intermediate (see [7], [8]). Unlike typical trypsin-like peptidases in which an acidic residue directly modulates the activity of the catalytic histidine residue, Glu1023 may modulate the activity of His746 through the hydroxyl group of Ser745 in this enzyme (see [8]).

createdupdated
2014-04-042015-07-03


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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