PDBsum entry 1k32

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Hydrolase PDB id
Protein chains
(+ 0 more) 1023 a.a. *
Waters ×2394
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of the tricorn protease
Structure: Tricorn protease. Chain: a, b, c, d, e, f. Engineered: yes
Source: Thermoplasma acidophilum. Organism_taxid: 2303. Gene: ta1490. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Hexamer (from PQS)
2.00Å     R-factor:   0.245     R-free:   0.264
Authors: H.Brandstetter,J.-S.Kim,M.Groll,R.Huber
Key ref:
H.Brandstetter et al. (2001). Crystal structure of the tricorn protease reveals a protein disassembly line. Nature, 414, 466-470. PubMed id: 11719810 DOI: 10.1038/35106609
01-Oct-01     Release date:   05-Dec-01    
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Protein chains
Pfam   ArchSchema ?
P96086  (TRI_THEAC) -  Tricorn protease
1071 a.a.
1023 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     hydrolase activity     3 terms  


DOI no: 10.1038/35106609 Nature 414:466-470 (2001)
PubMed id: 11719810  
Crystal structure of the tricorn protease reveals a protein disassembly line.
H.Brandstetter, J.S.Kim, M.Groll, R.Huber.
The degradation of cytosolic proteins is carried out predominantly by the proteasome, which generates peptides of 7-9 amino acids long. These products need further processing. Recently, a proteolytic system was identified in the model organism Thermoplasma acidophilum that performs this processing. The hexameric core protein of this modular system, referred to as tricorn protease, is a 720K protease that is able to assemble further into a giant icosahedral capsid, as determined by electron microscopy. Here, we present the crystal structure of the tricorn protease at 2.0 A resolution. The structure reveals a complex mosaic protein whereby five domains combine to form one of six subunits, which further assemble to form the 3-2-symmetric core protein. The structure shows how the individual domains coordinate the specific steps of substrate processing, including channelling of the substrate to, and the product from, the catalytic site. Moreover, the structure shows how accessory protein components might contribute to an even more complex protein machinery that efficiently collects the tricorn-released products.
  Selected figure(s)  
Figure 1.
Figure 1: Structure of tricorn protease. a, Ribbon representation of tricorn protease viewed along the molecular three-fold axis. Individual subunits are distinguished by colour. The overall dimensions of the molecule are 160 within the plane normal to the three-fold axis and 88 parallel to it. The conically shaped central pore measures 45 in diameter at its entrance and 20 close to the centre of the molecule. All figures were prepared with the programs Molscript and Raster3D^18,19. b, Representation of the highlighted subunit of a using identical colour coding and a similar orientation. The residues forming the propeller lids are displayed as well as the catalytic residues H746 (C1, magenta) and S965 (C2, green). D936, positioned on the C2 domain, confers specificity for basic substrate residues in the active site of the diad-related subunit (compare with a).
Figure 2.
Figure 2: The active site of tricorn protease. a, Surface representation of the active site, colour coded according to its electrostatic potential. The 'cut-open' surface (green) indicates an overall acidic S1 site (red), highly basic S2'/S3' substrate-recognition sites (deep blue), and a slightly positive S4/S5 site. b, The surface charge distributions related to A2:D936 (provided by the diad-related subunit) and D966 (S1); R131 and R132 (S2'/S3'); and A2:R940 and K992 (S4/S5). The unprimed substrate residues (Phe-Lys) correspond to those experimentally determined from a TLCK complex. The primed residues (Arg-Gln-Tyr-O-) were modelled semi-empirically by fitting the solvent electron density in addition to energetic considerations, because solvent molecules are known to mimic substrate-binding sites20.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2001, 414, 466-470) copyright 2001.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23385464 S.O.Dahms, M.Kuester, C.Streb, C.Roth, N.Sträter, and M.E.Than (2013).
Localization and orientation of heavy-atom cluster compounds in protein crystals using molecular replacement.
  Acta Crystallogr D Biol Crystallogr, 69, 284-297.  
20676100 C.K.Chuang, B.Rockel, G.Seyit, P.J.Walian, A.M.Schönegge, J.Peters, P.H.Zwart, W.Baumeister, and B.K.Jap (2010).
Hybrid molecular structure of the giant protease tripeptidyl peptidase II.
  Nat Struct Mol Biol, 17, 990-996.
PDB code: 3lxu
20615447 P.Goettig, V.Magdolen, and H.Brandstetter (2010).
Natural and synthetic inhibitors of kallikrein-related peptidases (KLKs).
  Biochimie, 92, 1546-1567.  
19388144 D.Chen, J.Chai, P.J.Hart, and G.Zhong (2009).
Identifying catalytic residues in CPAF, a Chlamydia-secreted protease.
  Arch Biochem Biophys, 485, 16-23.  
19266066 V.Delfosse, E.Girard, C.Birck, M.Delmarcelle, M.Delarue, O.Poch, P.Schultz, and C.Mayer (2009).
Structure of the archaeal pab87 peptidase reveals a novel self-compartmentalizing protease family.
  PLoS ONE, 4, e4712.
PDB code: 2qmi
  19064254 Z.Huang, Y.Feng, D.Chen, X.Wu, S.Huang, X.Wang, X.Xiao, W.Li, N.Huang, L.Gu, G.Zhong, and J.Chai (2008).
Structural basis for activation and inhibition of the secreted chlamydia protease CPAF.
  Cell Host Microbe, 4, 529-542.
PDB codes: 3dja 3dor 3dpm 3dpn
17964482 H.S.Lee, Y.Cho, Y.J.Kim, K.Nam, J.H.Lee, and S.G.Kang (2007).
Biochemical characterization of deblocking aminopeptidase from hyperthermophilic archaeon Thermococcus onnurineus NA1.
  J Biosci Bioeng, 104, 188-194.  
17242511 J.Bosch, T.Tamura, N.Tamura, W.Baumeister, and L.O.Essen (2007).
The beta-propeller domain of the trilobed protease from Pyrococcus furiosus reveals an open Velcro topology.
  Acta Crystallogr D Biol Crystallogr, 63, 179-187.
PDB code: 2gop
16834776 T.Cavalier-Smith (2006).
Rooting the tree of life by transition analyses.
  Biol Direct, 1, 19.  
15678420 M.Groll, M.Bochtler, H.Brandstetter, T.Clausen, and R.Huber (2005).
Molecular machines for protein degradation.
  Chembiochem, 6, 222-256.  
15659099 M.Verhaest, W.V.Ende, K.L.Roy, C.J.De Ranter, A.V.Laere, and A.Rabijns (2005).
X-ray diffraction structure of a plant glycosyl hydrolase family 32 protein: fructan 1-exohydrolase IIa of Cichorium intybus.
  Plant J, 41, 400-411.
PDB code: 1st8
15994304 P.Goettig, H.Brandstetter, M.Groll, W.Göhring, P.V.Konarev, D.I.Svergun, R.Huber, and J.S.Kim (2005).
X-ray snapshots of peptide processing in mutants of tricorn-interacting factor F1 from Thermoplasma acidophilum.
  J Biol Chem, 280, 33387-33396.
PDB codes: 1xqv 1xqw 1xqx 1xqy 1xrl 1xrm 1xrn 1xro 1xrp 1xrq 1xrr
15592905 F.Liu, S.Tachibana, T.Taira, M.Ishihara, F.Kato, and M.Yasuda (2004).
Purification and characterization of a high molecular mass serine carboxypeptidase from Monascus pilosus.
  J Ind Microbiol Biotechnol, 31, 572-580.  
15375159 S.Russo, and U.Baumann (2004).
Crystal structure of a dodecameric tetrahedral-shaped aminopeptidase.
  J Biol Chem, 279, 51275-51281.
PDB code: 1xfo
15103124 T.Hino, E.Kanamori, J.R.Shen, and T.Kouyama (2004).
An icosahedral assembly of the light-harvesting chlorophyll a/b protein complex from pea chloroplast thylakoid membranes.
  Acta Crystallogr D Biol Crystallogr, 60, 803-809.
PDB code: 1vcr
12655644 B.Eisenhaber, S.Maurer-Stroh, M.Novatchkova, G.Schneider, and F.Eisenhaber (2003).
Enzymes and auxiliary factors for GPI lipid anchor biosynthesis and post-translational transfer to proteins.
  Bioessays, 25, 367-385.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
12399461 G.P.Bertenshaw, M.T.Norcum, and J.S.Bond (2003).
Structure of homo- and hetero-oligomeric meprin metalloproteases. Dimers, tetramers, and high molecular mass multimers.
  J Biol Chem, 278, 2522-2532.  
12690074 M.Engel, T.Hoffmann, L.Wagner, M.Wermann, U.Heiser, R.Kiefersauer, R.Huber, W.Bode, H.U.Demuth, and H.Brandstetter (2003).
The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism.
  Proc Natl Acad Sci U S A, 100, 5063-5068.
PDB codes: 1orv 1orw
11980710 B.Franzetti, G.Schoehn, J.F.Hernandez, M.Jaquinod, R.W.Ruigrok, and G.Zaccai (2002).
Tetrahedral aminopeptidase: a novel large protease complex from archaea.
  EMBO J, 21, 2132-2138.  
12437101 H.Brandstetter, J.S.Kim, M.Groll, P.Göttig, and R.Huber (2002).
Structural basis for the processive protein degradation by tricorn protease.
  Biol Chem, 383, 1157-1165.  
12374735 P.Goettig, M.Groll, J.S.Kim, R.Huber, and H.Brandstetter (2002).
Structures of the tricorn-interacting aminopeptidase F1 with different ligands explain its catalytic mechanism.
  EMBO J, 21, 5343-5352.
PDB codes: 1mt3 1mtz 1mu0
11919638 T.Krojer, M.Garrido-Franco, R.Huber, M.Ehrmann, and T.Clausen (2002).
Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine.
  Nature, 416, 455-459.
PDB code: 1ky9
11937049 Z.Jawad, and M.Paoli (2002).
Novel sequences propel familiar folds.
  Structure, 10, 447-454.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.