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PDBsum entry 1the

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Hydrolase/hydrolase inhibitor PDB id
1the
Jmol
Contents
Protein chains
253 a.a. *
Ligands
0E6 ×2
Waters ×238
* Residue conservation analysis
PDB id:
1the
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structures of recombinant rat cathepsin b and a cath inhibitor complex: implications for structure-based inhibit
Structure: Cathepsin b. Chain: a, b. Synonym: cathepsin b1, rsg-2, cathepsin b light chain, cath heavy chain. Engineered: yes. Mutation: yes. Other_details: recombinant rat enzyme
Source: Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: cdna, ctsb. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.170    
Authors: C.P.Huber,Z.Jia
Key ref: Z.Jia et al. (1995). Crystal structures of recombinant rat cathepsin B and a cathepsin B-inhibitor complex. Implications for structure-based inhibitor design. J Biol Chem, 270, 5527-5533. PubMed id: 7890671
Date:
15-Sep-95     Release date:   10-Mar-96    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00787  (CATB_RAT) -  Cathepsin B
Seq:
Struc:
339 a.a.
253 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.22.1  - 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     proteolysis   1 term 
  Biochemical function     cysteine-type peptidase activity     1 term  

 

 
J Biol Chem 270:5527-5533 (1995)
PubMed id: 7890671  
 
 
Crystal structures of recombinant rat cathepsin B and a cathepsin B-inhibitor complex. Implications for structure-based inhibitor design.
Z.Jia, S.Hasnain, T.Hirama, X.Lee, J.S.Mort, R.To, C.P.Huber.
 
  ABSTRACT  
 
The lysosomal cysteine proteinase cathepsin B (EC 3.4.22.1) plays an important role in protein catabolism and has also been implicated in various disease states. The crystal structures of two forms of native recombinant rat cathepsin B have been determined. The overall folding of rat cathepsin B was shown to be very similar to that of the human liver enzyme. The structure of the native enzyme containing an underivatized active site cysteine (Cys29) showed the active enzyme conformation to be similar to that determined previously for the oxidized form. In a second structure Cys29 was derivatized with the reversible blocking reagent pyridyl disulfide. In this structure large side chain conformational changes were observed for the two key catalytic residues Cys29 and His199, demonstrating the potential flexibility of these side chains. In addition the structure of the complex between rat cathepsin B and the inhibitor benzyloxycarbonyl-Arg-Ser(O-Bzl) chloromethylketone was determined. The complex structure showed that very little conformational change occurs in the enzyme upon inhibitor binding. It also allowed visualization of the interaction between the enzyme and inhibitor. In particular the interaction between Glu245 and the P2 Arg residue was clearly demonstrated, and it was found that the benzyl group of the P1 substrate residue occupies a large hydrophobic pocket thought to represent the S'1 subsite. This may have important implications for structure-based design of cathepsin B inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19225106 Q.Yao, J.Cui, Y.Zhu, G.Wang, L.Hu, C.Long, R.Cao, X.Liu, N.Huang, S.Chen, L.Liu, and F.Shao (2009).
A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle.
  Proc Natl Acad Sci U S A, 106, 3716-3721.
PDB codes: 3eir 3eit
17617796 E.Wieczerzak, S.Rodziewicz-Motowidło, E.Jankowska, A.Giełdoń, and J.Ciarkowski (2007).
An enormously active and selective azapeptide inhibitor of cathepsin B.
  J Pept Sci, 13, 536-543.  
16650055 E.Wieczerzak, E.Jankowska, S.Rodziewicz-Motowidło, A.Giełdoń, J.Lagiewka, Z.Grzonka, M.Abrahamson, A.Grubb, and D.Brömme (2005).
Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B.
  J Pept Res, 66, 1.  
16231289 H.Li, A.D.Robertson, and J.H.Jensen (2005).
Very fast empirical prediction and rationalization of protein pKa values.
  Proteins, 61, 704-721.  
14694194 M.Zhu, F.Shao, R.W.Innes, J.E.Dixon, and Z.Xu (2004).
The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site.
  Proc Natl Acad Sci U S A, 101, 302-307.
PDB code: 1ukf
15009216 W.A.Judice, L.Puzer, S.S.Cotrin, A.K.Carmona, G.H.Coombs, L.Juliano, and M.A.Juliano (2004).
Carboxydipeptidase activities of recombinant cysteine peptidases. Cruzain of Trypanosoma cruzi and CPB of Leishmania mexicana.
  Eur J Biochem, 271, 1046-1053.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
12833545 M.Sulpizi, A.Laio, J.VandeVondele, A.Cattaneo, U.Rothlisberger, and P.Carloni (2003).
Reaction mechanism of caspases: insights from QM/MM Car-Parrinello simulations.
  Proteins, 52, 212-224.  
12668429 M.Sulpizi, U.Rothlisberger, and P.Carloni (2003).
Molecular dynamics studies of caspase-3.
  Biophys J, 84, 2207-2215.  
12454480 R.Reutzel, S.K.Boehlein, L.Govindasamy, R.B.Brenes, M.Agbandje-McKenna, S.M.Schuster, and R.McKenna (2002).
Crystallization and preliminary X-ray analysis of the tumor metastasis factor p37.
  Acta Crystallogr D Biol Crystallogr, 58, 2141-2144.  
11598875 D.Peters, and J.Peters (2001).
The pseudomolecule method and the structure of globular proteins. II. The example of ribonuclease F1 and T1.
  Biopolymers, 59, 402-410.  
10716634 R.I.Brinkworth, J.F.Tort, P.J.Brindley, and J.P.Dalton (2000).
Phylogenetic relationships and theoretical model of human cathepsin W (lymphopain), a cysteine proteinase from cytotoxic T lymphocytes.
  Int J Biochem Cell Biol, 32, 373-384.  
9914503 C.Serveau, G.Lalmanach, I.Hirata, J.Scharfstein, M.A.Juliano, and F.Gauthier (1999).
Discrimination of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, and mammalian cathepsins B and L, by a pH-inducible fluorogenic substrate of trypanosomal cysteine proteinases.
  Eur J Biochem, 259, 275-280.  
10089358 O.Carugo, and P.Argos (1999).
Reliability of atomic displacement parameters in protein crystal structures.
  Acta Crystallogr D Biol Crystallogr, 55, 473-478.  
  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.  
  9655332 M.E.McGrath, J.T.Palmer, D.Brömme, and J.R.Somoza (1998).
Crystal structure of human cathepsin S.
  Protein Sci, 7, 1294-1302.  
9015749 D.A.Giegel (1997).
ICE processing and kinetic mechanism.
  J Cell Biochem, 64, 11-18.  
9362483 R.Tikkanen, M.Peltola, C.Oinonen, J.Rouvinen, and L.Peltonen (1997).
Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase.
  EMBO J, 16, 6684-6693.  
  9260273 S.A.Gillmor, C.S.Craik, and R.J.Fletterick (1997).
Structural determinants of specificity in the cysteine protease cruzain.
  Protein Sci, 6, 1603-1611.
PDB codes: 1aim 2aim
8973203 D.Maes, J.Bouckaert, F.Poortmans, L.Wyns, and Y.Looze (1996).
Structure of chymopapain at 1.7 A resolution.
  Biochemistry, 35, 16292-16298.
PDB code: 1yal
8740363 M.Cygler, J.Sivaraman, P.Grochulski, R.Coulombe, A.C.Storer, and J.S.Mort (1996).
Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion.
  Structure, 4, 405-416.
PDB code: 1mir
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 codes are shown on the right.