PDBsum entry 1pbh

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protein links
Thiol protease PDB id
Jmol PyMol
Protein chain
317 a.a. *
* Residue conservation analysis
PDB id:
Name: Thiol protease
Title: Crystal structure of human recombinant procathepsin b at 3.2 angstrom resolution
Structure: Procathepsin b. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Expressed in: escherichia coli. Expression_system_taxid: 562.
3.20Å     R-factor:   0.216     R-free:   0.252
Authors: M.Podobnik,D.Turk
Key ref: D.Turk et al. (1996). Crystal structures of human procathepsin B at 3.2 and 3.3 Angstroms resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide. FEBS Lett, 384, 211-214. PubMed id: 8617355 DOI: 10.1016/0014-5793(96)00309-2
14-Feb-97     Release date:   25-Feb-98    
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Protein chain
Pfam   ArchSchema ?
P07858  (CATB_HUMAN) -  Cathepsin B
339 a.a.
317 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Cathepsin B.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of catalytic activity   2 terms 
  Biochemical function     cysteine-type peptidase activity     2 terms  


DOI no: 10.1016/0014-5793(96)00309-2 FEBS Lett 384:211-214 (1996)
PubMed id: 8617355  
Crystal structures of human procathepsin B at 3.2 and 3.3 Angstroms resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide.
D.Turk, M.Podobnik, R.Kuhelj, M.Dolinar, V.Turk.
A wild-type human procathepsin B was expressed, crystallized in two crystal forms and its crystal structure determined at 3.2 and 3.3 Angstroms resolution. The structure reveals that the propeptide folds on the cathepsin B surface, shielding the enzyme active site from exposure to solvent. The structure of the enzymatically active domains is virtually identical to that of the native enzyme [Musil et al. (1991) EMBO J. 10, 2321-2330]: the main difference is that the occluding loop residues are lifted above the body of the mature enzyme, supporting the propeptide structure.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21193411 A.Tochowicz, P.Goettig, R.Evans, R.Visse, Y.Shitomi, R.Palmisano, N.Ito, K.Richter, K.Maskos, D.Franke, D.Svergun, H.Nagase, W.Bode, and Y.Itoh (2011).
The Dimer Interface of the Membrane Type 1 Matrix Metalloproteinase Hemopexin Domain: CRYSTAL STRUCTURE AND BIOLOGICAL FUNCTIONS.
  J Biol Chem, 286, 7587-7600.
PDB code: 3c7x
19656187 B.Mirković, A.Premzl, V.Hodnik, B.Doljak, Z.Jevnikar, G.Anderluh, and J.Kos (2009).
Regulation of cathepsin B activity by 2A2 monoclonal antibody.
  FEBS J, 276, 4739-4751.  
19690370 J.Praaenikar, P.V.Afonine, G.Guncar, P.D.Adams, and D.Turk (2009).
Averaged kick maps: less noise, more signal... and probably less bias.
  Acta Crystallogr D Biol Crystallogr, 65, 921-931.  
19143833 J.R.Pungercar, D.Caglic, M.Sajid, M.Dolinar, O.Vasiljeva, U.Pozgan, D.Turk, M.Bogyo, V.Turk, and B.Turk (2009).
Autocatalytic processing of procathepsin B is triggered by proenzyme activity.
  FEBS J, 276, 660-668.  
19479029 K.C.Pandey, D.T.Barkan, A.Sali, and P.J.Rosenthal (2009).
Regulatory elements within the prodomain of falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum.
  PLoS One, 4, e5694.  
18515357 I.Redzynia, A.Ljunggren, M.Abrahamson, J.S.Mort, J.C.Krupa, M.Jaskolski, and G.Bujacz (2008).
Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin B.
  J Biol Chem, 283, 22815-22825.
PDB codes: 3cbj 3cbk
18796695 P.Schenker, P.Alfarano, P.Kolb, A.Caflisch, and A.Baici (2008).
A double-headed cathepsin B inhibitor devoid of warhead.
  Protein Sci, 17, 2145-2155.  
17403677 C.M.Stack, S.Donnelly, J.Lowther, W.Xu, P.R.Collins, L.S.Brinen, and J.P.Dalton (2007).
The major secreted cathepsin L1 protease of the liver fluke, Fasciola hepatica: a Leu-12 to Pro-12 replacement in the nonconserved C-terminal region of the prosegment prevents complete enzyme autoactivation and allows definition of the molecular events in prosegment removal.
  J Biol Chem, 282, 16532-16543.  
17726009 D.Caglic, J.R.Pungercar, G.Pejler, V.Turk, and B.Turk (2007).
Glycosaminoglycans facilitate procathepsin B activation through disruption of propeptide-mature enzyme interactions.
  J Biol Chem, 282, 33076-33085.  
17878156 P.Geraghty, C.M.Greene, M.O'Mahony, S.J.O'Neill, C.C.Taggart, and N.G.McElvaney (2007).
Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression.
  J Biol Chem, 282, 33389-33395.  
16895470 A.Baici, K.Müntener, A.Willimann, and R.Zwicky (2006).
Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death.
  Biol Chem, 387, 1017-1021.  
15657038 K.Müntener, A.Willimann, R.Zwicky, B.Svoboda, L.Mach, and A.Baici (2005).
Folding competence of N-terminally truncated forms of human procathepsin B.
  J Biol Chem, 280, 11973-11980.  
15195995 A.Rossi, Q.Deveraux, B.Turk, and A.Sali (2004).
Comprehensive search for cysteine cathepsins in the human genome.
  Biol Chem, 385, 363-372.  
14585834 D.H.Ebert, S.A.Kopecky-Bromberg, and T.S.Dermody (2004).
Cathepsin B Is Inhibited in Mutant Cells Selected during Persistent Reovirus Infection.
  J Biol Chem, 279, 3837-3851.  
15262981 K.Müntener, R.Zwicky, G.Csucs, J.Rohrer, and A.Baici (2004).
Exon skipping of cathepsin B: mitochondrial targeting of a lysosomal peptidase provokes cell death.
  J Biol Chem, 279, 41012-41017.  
14754899 P.R.Collins, C.M.Stack, S.M.O'Neill, S.Doyle, T.Ryan, G.P.Brennan, A.Mousley, M.Stewart, A.G.Maule, J.P.Dalton, and S.Donnelly (2004).
Cathepsin L1, the major protease involved in liver fluke (Fasciola hepatica) virulence: propetide cleavage sites and autoactivation of the zymogen secreted from gastrodermal cells.
  J Biol Chem, 279, 17038-17046.  
12887049 B.Turk, H.Fritz, and V.Turk (2003).
Vito Turk--30 years of research on cysteine proteases and their inhibitors.
  Biol Chem, 384, 833-836.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
11258881 C.Therrien, P.Lachance, T.Sulea, E.O.Purisima, H.Qi, E.Ziomek, A.Alvarez-Hernandez, W.R.Roush, and R.Ménard (2001).
Cathepsins X and B can be differentiated through their respective mono- and dipeptidyl carboxypeptidase activities.
  Biochemistry, 40, 2702-2711.  
11726493 D.Turk, V.Janjić, I.Stern, M.Podobnik, D.Lamba, S.W.Dahl, C.Lauritzen, J.Pedersen, V.Turk, and B.Turk (2001).
Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases.
  EMBO J, 20, 6570-6582.
PDB code: 1k3b
11322895 F.Lecaille, E.Authié, T.Moreau, C.Serveau, F.Gauthier, and G.Lalmanach (2001).
Subsite specificity of trypanosomal cathepsin L-like cysteine proteases. Probing the S2 pocket with phenylalanine-derived amino acids.
  Eur J Biochem, 268, 2733-2741.  
11517939 R.Ménard, C.Therrien, P.Lachance, T.Sulea, H.Qo, A.D.Alvarez-Hernandez, and W.R.Roush (2001).
Cathepsins X and B display distinct activity profiles that can be exploited for inhibitor design.
  Biol Chem, 382, 839-845.  
11532926 V.Turk, B.Turk, and D.Turk (2001).
Lysosomal cysteine proteases: facts and opportunities.
  EMBO J, 20, 4629-4633.  
11015218 B.Cigić, S.W.Dahl, and R.H.Pain (2000).
The residual pro-part of cathepsin C fulfills the criteria required for an intramolecular chaperone in folding and stabilizing the human proenzyme.
  Biochemistry, 39, 12382-12390.  
10998237 C.E.Carter, H.Marriage, and P.W.Goodenough (2000).
Mutagenesis and kinetic studies of a plant cysteine proteinase with an unusual arrangement of acidic amino acids in and around the active site.
  Biochemistry, 39, 11005-11013.  
10679409 R.J.Riese, and H.A.Chapman (2000).
Cathepsins and compartmentalization in antigen presentation.
  Curr Opin Immunol, 12, 107-113.  
10500110 A.R.Khan, N.Khazanovich-Bernstein, E.M.Bergmann, and M.N.James (1999).
Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors.
  Proc Natl Acad Sci U S A, 96, 10968-10975.  
10092883 B.Turk, I.Dolenc, B.Lenarcic, I.Krizaj, V.Turk, J.G.Bieth, and I.Björk (1999).
Acidic pH as a physiological regulator of human cathepsin L activity.
  Eur J Biochem, 259, 926-932.  
10022822 G.Guncar, G.Pungercic, I.Klemencic, V.Turk, and D.Turk (1999).
Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S.
  EMBO J, 18, 793-803.
PDB code: 1icf
  10048321 J.Sivaraman, M.Lalumière, R.Ménard, and M.Cygler (1999).
Crystal structure of wild-type human procathepsin K.
  Protein Sci, 8, 283-290.
PDB code: 7pck
10410800 M.E.McGrath (1999).
The lysosomal cysteine proteases.
  Annu Rev Biophys Biomol Struct, 28, 181-204.  
10213604 O.Quraishi, D.K.Nägler, T.Fox, J.Sivaraman, M.Cygler, J.S.Mort, and A.C.Storer (1999).
The occluding loop in cathepsin B defines the pH dependence of inhibition by its propeptide.
  Biochemistry, 38, 5017-5023.  
9776083 A.A.Sinha, B.J.Quast, M.J.Wilson, P.K.Reddy, D.F.Gleason, and B.F.Sloane (1998).
Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy.
  Anat Rec, 252, 281-289.  
  9568890 A.R.Khan, and M.N.James (1998).
Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes.
  Protein Sci, 7, 815-836.  
  9524065 D.Turk, G.Guncar, M.Podobnik, and B.Turk (1998).
Revised definition of substrate binding sites of papain-like cysteine proteases.
  Biol Chem, 379, 137-147.  
9493267 G.Guncar, M.Podobnik, J.Pungercar, B.Strukelj, V.Turk, and D.Turk (1998).
Crystal structure of porcine cathepsin H determined at 2.1 A resolution: location of the mini-chain C-terminal carboxyl group defines cathepsin H aminopeptidase function.
  Structure, 6, 51-61.
PDB code: 8pch
9737969 G.Lalmanach, F.Lecaille, J.R.Chagas, E.Authié, J.Scharfstein, M.A.Juliano, and F.Gauthier (1998).
Inhibition of trypanosomal cysteine proteinases by their propeptides.
  J Biol Chem, 273, 25112-25116.  
  9524060 M.T.Stubbs, M.Renatus, and W.Bode (1998).
An active zymogen: unravelling the mystery of tissue-type plasminogen activator.
  Biol Chem, 379, 95.  
9406551 A.R.Khan, M.M.Cherney, N.I.Tarasova, and M.N.James (1997).
Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin.
  Nat Struct Biol, 4, 1010-1015.
PDB code: 1avf
8995421 C.Illy, O.Quraishi, J.Wang, E.Purisima, T.Vernet, and J.S.Mort (1997).
Role of the occluding loop in cathepsin B activity.
  J Biol Chem, 272, 1197-1202.  
9461297 G.Maubach, K.Schilling, W.Rommerskirch, I.Wenz, J.E.Schultz, E.Weber, and B.Wiederanders (1997).
The inhibition of cathepsin S by its propeptide--specificity and mechanism of action.
  Eur J Biochem, 250, 745-750.  
9233788 S.C.Johnston, C.N.Larsen, W.J.Cook, K.D.Wilkinson, and C.P.Hill (1997).
Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution.
  EMBO J, 16, 3787-3796.
PDB code: 1uch
  9165062 W.Baumeister, Z.Cejka, M.Kania, and E.Seemüller (1997).
The proteasome: a macromolecular assembly designed to confine proteolysis to a nanocompartment.
  Biol Chem, 378, 121-130.  
8939744 M.R.Groves, M.A.Taylor, M.Scott, N.J.Cummings, R.W.Pickersgill, and J.A.Jenkins (1996).
The prosequence of procaricain forms an alpha-helical domain that prevents access to the substrate-binding cleft.
  Structure, 4, 1193-1203.
PDB code: 1pci
  8896443 R.Coulombe, P.Grochulski, J.Sivaraman, R.Ménard, J.S.Mort, and M.Cygler (1996).
Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment.
  EMBO J, 15, 5492-5503.
PDB code: 1cjl
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.