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PDBsum entry 3e1z

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protein ligands metals Protein-protein interface(s) links
Hydrolase inhibitor/hydrolase PDB id
3e1z
Jmol
Contents
Protein chains
109 a.a. *
212 a.a. *
Ligands
FMT ×10
ACY
Metals
_ZN
Waters ×298
* Residue conservation analysis
PDB id:
3e1z
Name: Hydrolase inhibitor/hydrolase
Title: Crystal structure of the parasite protesase inhibitor chagasin in complex with papain
Structure: Chagasin. Chain: a. Synonym: cysteine protease inhibitor. Engineered: yes. Papain. Chain: b. Synonym: cysteine protease, papaya proteinase i, ppi. Ec: 3.4.22.2
Source: Trypanosoma cruzi. Organism_taxid: 5693. Gene: cha. Expressed in: escherichia coli. Expression_system_taxid: 562. Carica papaya. Papaya. Organism_taxid: 3649. Strain: papaya
Resolution:
1.86Å     R-factor:   0.166     R-free:   0.208
Authors: I.Redzynia,G.Bujacz,A.Bujacz,A.Ljunggren,M.Abrahamson, M.Jaskolski
Key ref: I.Redzynia et al. (2009). Crystal structure of the parasite inhibitor chagasin in complex with papain allows identification of structural requirements for broad reactivity and specificity determinants for target proteases. FEBS J, 276, 793-806. PubMed id: 19143838
Date:
05-Aug-08     Release date:   27-Jan-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q966X9  (CHAG_TRYCR) -  Chagasin
Seq:
Struc:
110 a.a.
109 a.a.
Protein chain
Pfam   ArchSchema ?
P00784  (PAPA1_CARPA) -  Papain
Seq:
Struc:
345 a.a.
212 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain B: 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!
  Cellular component     cell surface   4 terms 
  Biological process     proteolysis   3 terms 
  Biochemical function     peptidase inhibitor activity     3 terms  

 

 
FEBS J 276:793-806 (2009)
PubMed id: 19143838  
 
 
Crystal structure of the parasite inhibitor chagasin in complex with papain allows identification of structural requirements for broad reactivity and specificity determinants for target proteases.
I.Redzynia, A.Ljunggren, A.Bujacz, M.Abrahamson, M.Jaskolski, G.Bujacz.
 
  ABSTRACT  
 
A complex of chagasin, a protein inhibitor from Trypanosoma cruzi, and papain, a classic family C1 cysteine protease, has been crystallized. Kinetic studies revealed that inactivation of papain by chagasin is very fast (k(on) = 1.5 x 10(6) M(-1) x s(-1)), and results in the formation of a very tight, reversible complex (K(i) = 36 pM), with similar or better rate and equilibrium constants than those for cathepsins L and B. The high-resolution crystal structure shows an inhibitory wedge comprising three loops, which forms a number of contacts responsible for the high-affinity binding. Comparison with the structure of papain in complex with human cystatin B reveals that, despite entirely different folding, the two inhibitors utilize very similar atomic interactions, leading to essentially identical affinities for the enzyme. Comparisons of the chagasin-papain complex with high-resolution structures of chagasin in complexes with cathepsin L, cathepsin B and falcipain allowed the creation of a consensus map of the structural features that are important for efficient inhibition of papain-like enzymes. The comparisons also revealed a number of unique interactions that can be used to design enzyme-specific inhibitors. As papain exhibits high structural similarity to the catalytic domain of the T. cruzi enzyme cruzipain, the present chagasin-papain complex provides a reliable model of chagasin-cruzipain interactions. Such information, coupled with our identification of specificity-conferring interactions, should be important for the development of drugs for treatment of the devastating Chagas disease caused by this parasite.
 

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
20860624 M.Renko, U.Požgan, D.Majera, and D.Turk (2010).
Stefin A displaces the occluding loop of cathepsin B only by as much as required to bind to the active site cleft.
  FEBS J, 277, 4338-4345.
PDB code: 3k9m
20231898 R.Bourgeas, M.J.Basse, X.Morelli, and P.Roche (2010).
Atomic analysis of protein-protein interfaces with known inhibitors: the 2P2I database.
  PLoS One, 5, e9598.  
20175878 R.Kolodziejczyk, K.Michalska, A.Hernandez-Santoyo, M.Wahlbom, A.Grubb, and M.Jaskolski (2010).
Crystal structure of human cystatin C stabilized against amyloid formation.
  FEBS J, 277, 1726-1737.
PDB code: 3gax
20012364 V.Heussler, A.Rennenberg, and R.Stanway (2010).
Host cell death induced by the egress of intracellular Plasmodium parasites.
  Apoptosis, 15, 376-385.  
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.