DB code: M00351

RLCP classification 1.13.30020.28 : Hydrolysis
CATH domain 2.120.10.60 : Neuraminidase
2.130.10.10 : Methylamine Dehydrogenase; Chain H
3.30.750.44 : Transcription Regulator spoIIAA Catalytic domain
2.30.42.10 : Pdz3 Domain
3.90.226.10 : 2-enoyl-CoA Hydratase; Chain A, domain 1 Catalytic domain
E.C. 3.4.21.- 3.4.25.1
CSA 1k32
M-CSA 1k32
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P96086 Tricorn protease
EC 3.4.21.-
NP_394941.1 (Protein)
NC_002578.1 (DNA/RNA sequence)
S41.005 (Serine)
PF07676 (PD40)
PF03572 (Peptidase_S41)
[Graphical View]

KEGG enzyme name
Proteasome 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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P96086 TRI_THEAC Part 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. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00012 I00087 I00085 I00086
E.C.
Compound Peptide Peptide Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein peptide/protein
ChEBI
PubChem
1k32A01 Unbound Unbound Unbound Unbound Unbound
1k32B01 Unbound Unbound Unbound Unbound Unbound
1k32C01 Unbound Unbound Unbound Unbound Unbound
1k32D01 Unbound Unbound Unbound Unbound Unbound
1k32E01 Unbound Unbound Unbound Unbound Unbound
1k32F01 Unbound Unbound Unbound Unbound Unbound
1n6dA01 Unbound Unbound Unbound Unbound Unbound
1n6dB01 Unbound Unbound Unbound Unbound Unbound
1n6dC01 Unbound Unbound Unbound Unbound Unbound
1n6dD01 Unbound Unbound Unbound Unbound Unbound
1n6dE01 Unbound Unbound Unbound Unbound Unbound
1n6dF01 Unbound Unbound Unbound Unbound Unbound
1n6eA01 Unbound Unbound Unbound Unbound Unbound
1n6eC01 Unbound Unbound Unbound Unbound Unbound
1n6eE01 Unbound Unbound Unbound Unbound Unbound
1n6eG01 Unbound Unbound Unbound Unbound Unbound
1n6eI01 Unbound Unbound Unbound Unbound Unbound
1n6eK01 Unbound Unbound Unbound Unbound Unbound
1n6fA01 Unbound Unbound Unbound Unbound Unbound
1n6fB01 Unbound Unbound Unbound Unbound Unbound
1n6fC01 Unbound Unbound Unbound Unbound Unbound
1n6fD01 Unbound Unbound Unbound Unbound Unbound
1n6fE01 Unbound Unbound Unbound Unbound Unbound
1n6fF01 Unbound Unbound Unbound Unbound Unbound
1k32A02 Unbound Unbound Unbound Unbound Unbound
1k32B02 Unbound Unbound Unbound Unbound Unbound
1k32C02 Unbound Unbound Unbound Unbound Unbound
1k32D02 Unbound Unbound Unbound Unbound Unbound
1k32E02 Unbound Unbound Unbound Unbound Unbound
1k32F02 Unbound Unbound Unbound Unbound Unbound
1n6dA02 Unbound Unbound Unbound Unbound Unbound
1n6dB02 Unbound Unbound Unbound Unbound Unbound
1n6dC02 Unbound Unbound Unbound Unbound Unbound
1n6dD02 Unbound Unbound Unbound Unbound Unbound
1n6dE02 Unbound Unbound Unbound Unbound Unbound
1n6dF02 Unbound Unbound Unbound Unbound Unbound
1n6eA02 Unbound Unbound Unbound Unbound Unbound
1n6eC02 Unbound Unbound Unbound Unbound Unbound
1n6eE02 Unbound Unbound Unbound Unbound Unbound
1n6eG02 Unbound Unbound Unbound Unbound Unbound
1n6eI02 Unbound Unbound Unbound Unbound Unbound
1n6eK02 Unbound Unbound Unbound Unbound Unbound
1n6fA02 Unbound Unbound Unbound Unbound Unbound
1n6fB02 Unbound Unbound Unbound Unbound Unbound
1n6fC02 Unbound Unbound Unbound Unbound Unbound
1n6fD02 Unbound Unbound Unbound Unbound Unbound
1n6fE02 Unbound Unbound Unbound Unbound Unbound
1n6fF02 Unbound Unbound Unbound Unbound Unbound
1k32A03 Unbound Unbound Unbound Unbound Unbound
1k32B03 Unbound Unbound Unbound Unbound Unbound
1k32C03 Unbound Unbound Unbound Unbound Unbound
1k32D03 Unbound Unbound Unbound Unbound Unbound
1k32E03 Unbound Unbound Unbound Unbound Unbound
1k32F03 Unbound Unbound Unbound Unbound Unbound
1n6dA03 Unbound Unbound Unbound Unbound Unbound
1n6dB03 Unbound Unbound Unbound Unbound Unbound
1n6dC03 Unbound Unbound Unbound Unbound Unbound
1n6dD03 Unbound Unbound Unbound Unbound Unbound
1n6dE03 Unbound Unbound Unbound Unbound Unbound
1n6dF03 Unbound Unbound Unbound Unbound Unbound
1n6eA03 Unbound Unbound Unbound Unbound Unbound
1n6eC03 Unbound Unbound Unbound Unbound Unbound
1n6eE03 Unbound Unbound Unbound Unbound Unbound
1n6eG03 Unbound Unbound Unbound Unbound Unbound
1n6eI03 Unbound Unbound Unbound Unbound Unbound
1n6eK03 Unbound Unbound Unbound Unbound Unbound
1n6fA03 Unbound Unbound Unbound Unbound Unbound
1n6fB03 Unbound Unbound Unbound Unbound Unbound
1n6fC03 Unbound Unbound Unbound Unbound Unbound
1n6fD03 Unbound Unbound Unbound Unbound Unbound
1n6fE03 Unbound Unbound Unbound Unbound Unbound
1n6fF03 Unbound Unbound Unbound Unbound Unbound
1k32A04 Unbound Unbound Unbound Unbound Unbound
1k32B04 Unbound Unbound Unbound Unbound Unbound
1k32C04 Unbound Unbound Unbound Unbound Unbound
1k32D04 Unbound Unbound Unbound Unbound Unbound
1k32E04 Unbound Unbound Unbound Unbound Unbound
1k32F04 Unbound Unbound Unbound Unbound Unbound
1n6dA04 Unbound Unbound Unbound Unbound Unbound
1n6dB04 Unbound Unbound Unbound Unbound Unbound
1n6dC04 Unbound Unbound Unbound Unbound Unbound
1n6dD04 Unbound Unbound Unbound Unbound Unbound
1n6dE04 Unbound Unbound Unbound Unbound Unbound
1n6dF04 Unbound Unbound Unbound Unbound Unbound
1n6eA04 Unbound Unbound Unbound Unbound Unbound
1n6eC04 Unbound Unbound Unbound Unbound Unbound
1n6eE04 Unbound Unbound Unbound Unbound Unbound
1n6eG04 Unbound Unbound Unbound Unbound Unbound
1n6eI04 Unbound Unbound Unbound Unbound Unbound
1n6eK04 Unbound Unbound Unbound Unbound Unbound
1n6fA04 Unbound Unbound Unbound Unbound Unbound
1n6fB04 Unbound Unbound Unbound Unbound Unbound
1n6fC04 Unbound Unbound Unbound Unbound Unbound
1n6fD04 Unbound Unbound Unbound Unbound Unbound
1n6fE04 Unbound Unbound Unbound Unbound Unbound
1n6fF04 Unbound Unbound Unbound Unbound Unbound
1k32A05 Unbound Unbound Unbound Unbound Unbound
1k32B05 Unbound Unbound Unbound Unbound Unbound
1k32C05 Unbound Unbound Unbound Unbound Unbound
1k32D05 Unbound Unbound Unbound Unbound Unbound
1k32E05 Unbound Unbound Unbound Unbound Unbound
1k32F05 Unbound Unbound Unbound Unbound Unbound
1n6dA05 Unbound Unbound Unbound Intermediate-analogue:ARG-VAL-ARG-LYS (chain G) Unbound
1n6dB05 Unbound Unbound Unbound Intermediate-analogue:ARG-VAL-ARG-LYS (chain H) Unbound
1n6dC05 Unbound Unbound Unbound Intermediate-analogue:ARG-VAL-ARG-LYS (chain I) Unbound
1n6dD05 Unbound Unbound Unbound Intermediate-analogue:ARG-VAL-ARG-LYS (chain J) Unbound
1n6dE05 Unbound Unbound Unbound Intermediate-analogue:ARG-VAL-ARG-LYS (chain K) Unbound
1n6dF05 Unbound Unbound Unbound Intermediate-analogue:ARG-VAL-ARG-LYS (chain L) Unbound
1n6eA05 Unbound Unbound Unbound Unbound Transition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE (chain B)
1n6eC05 Unbound Unbound Unbound Unbound Transition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE (chain D)
1n6eE05 Unbound Unbound Unbound Unbound Transition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE (chain F)
1n6eG05 Unbound Unbound Unbound Unbound Transition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE (chain H)
1n6eI05 Unbound Unbound Unbound Unbound Transition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE (chain J)
1n6eK05 Unbound Unbound Unbound Unbound Transition-state-analogue:THR-GLN-LYS-ALA-ALA-ALA-GLU-LEU-THR-PHE-PHE (chain L)
1n6fA05 Unbound Unbound Transition-state-analogue:DKT Unbound Unbound
1n6fB05 Unbound Unbound Transition-state-analogue:DKT Unbound Unbound
1n6fC05 Unbound Unbound Transition-state-analogue:DKT Unbound Unbound
1n6fD05 Unbound Unbound Transition-state-analogue:DKT Unbound Unbound
1n6fE05 Unbound Unbound Transition-state-analogue:DKT Unbound Unbound
1n6fF05 Unbound Unbound Transition-state-analogue:DKT Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [7],[8],[9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
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
1k32A03 SER 745;HIS 746
1k32B03 SER 745;HIS 746
1k32C03 SER 745;HIS 746
1k32D03 SER 745;HIS 746
1k32E03 SER 745;HIS 746
1k32F03 SER 745;HIS 746
1n6dA03 SER 745;HIS 746
1n6dB03 SER 745;HIS 746
1n6dC03 SER 745;HIS 746
1n6dD03 SER 745;HIS 746
1n6dE03 SER 745;HIS 746
1n6dF03 SER 745;HIS 746
1n6eA03 SER 745;HIS 746
1n6eC03 SER 745;HIS 746
1n6eE03 SER 745;HIS 746
1n6eG03 SER 745;HIS 746
1n6eI03 SER 745;HIS 746
1n6eK03 SER 745;HIS 746
1n6fA03 SER 745;HIS 746
1n6fB03 SER 745;HIS 746
1n6fC03 SER 745;HIS 746
1n6fD03 SER 745;HIS 746
1n6fE03 SER 745;HIS 746
1n6fF03 SER 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
1k32A05 SER 965;GLU 1023 GLY 918;ASP 966
1k32B05 SER 965;GLU 1023 GLY 918;ASP 966
1k32C05 SER 965;GLU 1023 GLY 918;ASP 966
1k32D05 SER 965;GLU 1023 GLY 918;ASP 966
1k32E05 SER 965;GLU 1023 GLY 918;ASP 966
1k32F05 SER 965;GLU 1023 GLY 918;ASP 966
1n6dA05 SER 965;GLU 1023 GLY 918;ASP 966
1n6dB05 SER 965;GLU 1023 GLY 918;ASP 966
1n6dC05 SER 965;GLU 1023 GLY 918;ASP 966
1n6dD05 SER 965;GLU 1023 GLY 918;ASP 966
1n6dE05 SER 965;GLU 1023 GLY 918;ASP 966
1n6dF05 SER 965;GLU 1023 GLY 918;ASP 966
1n6eA05 SER 965;GLU 1023 GLY 918;ASP 966
1n6eC05 SER 965;GLU 1023 GLY 918;ASP 966
1n6eE05 SER 965;GLU 1023 GLY 918;ASP 966
1n6eG05 SER 965;GLU 1023 GLY 918;ASP 966
1n6eI05 SER 965;GLU 1023 GLY 918;ASP 966
1n6eK05 SER 965;GLU 1023 GLY 918;ASP 966
1n6fA05 SER 965;GLU 1023 GLY 918;ASP 966
1n6fB05 SER 965;GLU 1023 GLY 918;ASP 966
1n6fC05 SER 965;GLU 1023 GLY 918;ASP 966
1n6fD05 SER 965;GLU 1023 GLY 918;ASP 966
1n6fE05 SER 965;GLU 1023 GLY 918;ASP 966
1n6fF05 SER 965;GLU 1023 GLY 918;ASP 966

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[7]
p.467
[8]
p.1159-1161
[9]
p.1047

References
[1]
Resource
Comments
Medline ID
PubMed ID 8910281
Journal Science
Year 1996
Volume 274
Pages 1385-9
Authors Tamura T, Tamura N, Cejka Z, Hegerl R, Lottspeich F, Baumeister W
Title Tricorn protease--the core of a modular proteolytic system.
Related PDB
Related UniProtKB
[2]
Resource
Comments THREE-DIMENSIONAL RECONSTRUCTION FROM ELECTRON MICROGRAPHS.
Medline ID
PubMed ID 9659903
Journal Mol Cell
Year 1997
Volume 1
Pages 59-65
Authors Walz J, Tamura T, Tamura N, Grimm R, Baumeister W, Koster AJ
Title Tricorn protease exists as an icosahedral supermolecule in vivo.
Related PDB
Related UniProtKB
[3]
Resource
Comments CHARACTERIZATION OF PROTEIN INTERACTION.
Medline ID
PubMed ID 9845366
Journal Cell
Year 1998
Volume 95
Pages 637-48
Authors Tamura N, Lottspeich F, Baumeister W, Tamura T
Title The role of tricorn protease and its aminopeptidase-interacting factors in cellular protein degradation.
Related PDB
Related UniProtKB
[4]
Resource
Comments DOMAINS.
Medline ID
PubMed ID 10518749
Journal FEMS Microbiol Lett
Year 1999
Volume 179
Pages 447-51
Authors Ponting CP, Pallen MJ
Title beta-propeller repeats and a PDZ domain in the tricorn protease: predicted self-compartmentalisation and C-terminal polypeptide-binding strategies of substrate selection.
Related PDB
Related UniProtKB
[5]
Resource
Comments THREE-DIMENSIONAL RECONSTRUCTION (1.3 NM) BY ELECTRON CRYOMICROSCOPY.
Medline ID
PubMed ID 10600560
Journal J Struct Biol
Year 1999
Volume 128
Pages 65-8
Authors Walz J, Koster AJ, Tamura T, Baumeister W
Title Capsids of tricorn protease studied by electron cryomicroscopy.
Related PDB
Related UniProtKB
[6]
Resource
Comments CRYSTALLIZATION.
Medline ID
PubMed ID 11469880
Journal J Struct Biol
Year 2001
Volume 134
Pages 83-7
Authors Bosch J, Tamura T, Bourenkov G, Baumeister W, Essen LO
Title Purification, crystallization, and preliminary X-ray diffraction analysis of the Tricorn protease hexamer from Thermoplasma acidophilum.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), MUTAGENESIS OF 131-ARG-ARG-132; HIS-746 AND SER-965.
Medline ID
PubMed ID 11719810
Journal Nature
Year 2001
Volume 414
Pages 466-70
Authors Brandstetter H, Kim JS, Groll M, Huber R
Title Crystal structure of the tricorn protease reveals a protein disassembly line.
Related PDB 1k32
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 12437101
Journal Biol Chem
Year 2002
Volume 383
Pages 1157-65
Authors Brandstetter H, Kim JS, Groll M, Gottig P, Huber R
Title Structural basis for the processive protein degradation by tricorn protease.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID
PubMed ID 12470958
Journal J Mol Biol
Year 2002
Volume 324
Pages 1041-50
Authors Kim JS, Groll M, Musiol HJ, Behrendt R, Kaiser M, Moroder L, Huber R, Brandstetter H
Title Navigation inside a protease: substrate selection and product exit in the tricorn protease from Thermoplasma acidophilum.
Related PDB 1n6d 1n6e 1n6f
Related UniProtKB

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]).

Created Updated
2014-04-04 2015-07-03