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PDBsum entry 1cvz

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Hydrolase PDB id
1cvz
Jmol
Contents
Protein chain
212 a.a. *
Ligands
C48
Waters ×129
* Residue conservation analysis
PDB id:
1cvz
Name: Hydrolase
Title: Crystal structure analysis of papain with clik148(cathepsin l specific inhibitor)
Structure: Papain. Chain: a. Fragment: residues 134-345. Ec: 3.4.22.2
Source: Carica papaya. Papaya. Organism_taxid: 3649
Resolution:
1.70Å     R-factor:   0.177     R-free:   0.214
Authors: H.Tsuge
Key ref: H.Tsuge et al. (1999). Inhibition mechanism of cathepsin L-specific inhibitors based on the crystal structure of papain-CLIK148 complex. Biochem Biophys Res Commun, 266, 411-416. PubMed id: 10600517 DOI: 10.1006/bbrc.1999.1830
Date:
24-Aug-99     Release date:   30-Aug-00    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00784  (PAPA1_CARPA) -  Papain
Seq:
Struc:
345 a.a.
212 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.22.2  - Papain.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins with broad specificity for peptide bonds, with preference for a residue bearing a large hydrophobic sidechain at the P2 position. Does not accept Val at P1'.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     cysteine-type peptidase activity     1 term  

 

 
DOI no: 10.1006/bbrc.1999.1830 Biochem Biophys Res Commun 266:411-416 (1999)
PubMed id: 10600517  
 
 
Inhibition mechanism of cathepsin L-specific inhibitors based on the crystal structure of papain-CLIK148 complex.
H.Tsuge, T.Nishimura, Y.Tada, T.Asao, D.Turk, V.Turk, N.Katunuma.
 
  ABSTRACT  
 
Papain was used as an experimental model structure to understand the inhibition mechanism of newly developed specific inhibitors of cathepsin L, the papain superfamily. Recently, we developed a series of cathepsin L-specific inhibitors which are called the CLIK series [(1999) FEBS Lett. 458, 6-10]. Here, we report the complex structure of papain with CLIK148, which is a representative inhibitor from the CLIK series. The inhibitor complex structure was solved at 1.7 A resolution with conventional R 0.177. Unlike other epoxisuccinate inhibitors (E64, CA030, and CA074), CLIK148 uses both prime and nonprime sites, which are important for the specific inhibitory effect on cathepsin L. Also, the specificity for cathepsin L could be explained by the existence of Phe in the P2 site and hydrophobic interaction of N-terminal pyridine ring.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21326229 M.A.Adams-Cioaba, J.C.Krupa, C.Xu, J.S.Mort, and J.Min (2011).
Structural basis for the recognition and cleavage of histone H3 by cathepsin L.
  Nat Commun, 2, 197.
PDB codes: 3iv2 3k24
20877570 A.Yamada, N.Ishimaru, R.Arakaki, N.Katunuma, and Y.Hayashi (2010).
Cathepsin L inhibition prevents murine autoimmune diabetes via suppression of CD8(+) T cell activity.
  PLoS One, 5, e12894.  
20980477 H.Kido, and K.Ishidoh (2010).
Nobuhiko Katunuma: an outstanding scientist in the field of proteolysis and warm-hearted 'Kendo Fighter' biochemist.
  J Biochem, 148, 527-531.  
19807666 D.M.Huryn, and A.B.Smith (2009).
The identification, characterization and optimization of small molecule probes of cysteine proteases: experiences of the Penn Center for Molecular Discovery with cathepsin B and cathepsin L.
  Curr Top Med Chem, 9, 1206-1216.  
19252298 K.Takahashi, T.Ueno, I.Tanida, N.Minematsu-Ikeguchi, M.Murata, and E.Kominami (2009).
Characterization of CAA0225, a Novel Inhibitor Specific for Cathepsin L, as a Probe for Autophagic Proteolysis.
  Biol Pharm Bull, 32, 475-479.  
19670215 Z.Jevnikar, N.Obermajer, and J.Kos (2009).
Cysteine protease-mediated cytoskeleton interactions with LFA-1 promote T-cell morphological changes.
  Cell Motil Cytoskeleton, 66, 1030-1040.  
18499453 M.C.Myers, P.P.Shah, M.P.Beavers, A.D.Napper, S.L.Diamond, A.B.Smith, and D.M.Huryn (2008).
Design, synthesis, and evaluation of inhibitors of cathepsin L: Exploiting a unique thiocarbazate chemotype.
  Bioorg Med Chem Lett, 18, 3646-3651.  
18598021 M.P.Beavers, M.C.Myers, P.P.Shah, J.E.Purvis, S.L.Diamond, B.S.Cooperman, D.M.Huryn, and A.B.Smith (2008).
Molecular docking of cathepsin L inhibitors in the binding site of papain.
  J Chem Inf Model, 48, 1464-1472.  
18403718 P.P.Shah, M.C.Myers, M.P.Beavers, J.E.Purvis, H.Jing, H.J.Grieser, E.R.Sharlow, A.D.Napper, D.M.Huryn, B.S.Cooperman, A.B.Smith, and S.L.Diamond (2008).
Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L.
  Mol Pharmacol, 74, 34-41.  
16286017 H.Kitamura, H.Kamon, S.Sawa, S.J.Park, N.Katunuma, K.Ishihara, M.Murakami, and T.Hirano (2005).
IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells.
  Immunity, 23, 491-502.  
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
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.  
12887055 N.Katunuma, Y.Matsunaga, K.Himeno, and Y.Hayashi (2003).
Insights into the roles of cathepsins in antigen processing and presentation revealed by specific inhibitors.
  Biol Chem, 384, 883-890.  
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.