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PDBsum entry 2oz2
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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
2oz2

 

 

 

 

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Contents
Protein chains
215 a.a. *
Ligands
SO4 ×8
D1R ×2
Waters ×261
* Residue conservation analysis
PDB id:
2oz2
Name: Hydrolase
Title: Crystal structure analysis of cruzain bound to vinyl sulfone derived inhibitor (k11777)
Structure: Cruzipain. Chain: a, c. Fragment: cruzain (residues 123-337). Synonym: major cysteine proteinase, cruzaine. Engineered: yes
Source: Trypanosoma cruzi. Organism_taxid: 5693. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
1.95Å     R-factor:   0.159     R-free:   0.207
Authors: M.Rickert,L.Brinen
Key ref:
I.D.Kerr et al. (2009). Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J Biol Chem, 284, 25697-25703. PubMed id: 19620707 DOI: 10.1074/jbc.M109.014340
Date:
23-Feb-07     Release date:   26-Feb-08    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P25779  (CYSP_TRYCR) -  Cruzipain from Trypanosoma cruzi
Seq:
Struc: 		467 a.a.
215 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.22.51  - cruzipain.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1074/jbc.M109.014340 J Biol Chem 284:25697-25703 (2009)
PubMed id: 19620707  
 
 
Vinyl sulfones as antiparasitic agents and a structural basis for drug design.
I.D.Kerr, J.H.Lee, C.J.Farady, R.Marion, M.Rickert, M.Sajid, K.C.Pandey, C.R.Caffrey, J.Legac, E.Hansell, J.H.McKerrow, C.S.Craik, P.J.Rosenthal, L.S.Brinen.
 
  ABSTRACT  
 
Cysteine proteases of the papain superfamily are implicated in a number of cellular processes and are important virulence factors in the pathogenesis of parasitic disease. These enzymes have therefore emerged as promising targets for antiparasitic drugs. We report the crystal structures of three major parasite cysteine proteases, cruzain, falcipain-3, and the first reported structure of rhodesain, in complex with a class of potent, small molecule, cysteine protease inhibitors, the vinyl sulfones. These data, in conjunction with comparative inhibition kinetics, provide insight into the molecular mechanisms that drive cysteine protease inhibition by vinyl sulfones, the binding specificity of these important proteases and the potential of vinyl sulfones as antiparasitic drugs.
 
  Selected figure(s)  
 
Figure 1.
The structures of cruzain, rhodesain, and falcipain-3. Ribbon representation and superimposition of cruzain (pink), rhodesain (aquamarine), and falcipain-3 (yellow) are shown. Insertions in falcipain-3 are colored purple. All structure figures were prepared in PyMOL (DeLano, 2002). 		Figure 3.
The active sites of cruzain (A), rhodesain (B), and falcipain-3 (C).Ball and stick representation shows the conserved catalytic triad and other important residues. The figure is colored as in Fig. 1 with each inhibitor in gray.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 25697-25703) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21275051 V.Ehmke, C.Heindl, M.Rottmann, C.Freymond, W.B.Schweizer, R.Brun, A.Stich, T.Schirmeister, and F.Diederich (2011).
Potent and selective inhibition of cysteine proteases from Plasmodium falciparum and Trypanosoma brucei.
  ChemMedChem, 6, 273-278.  
20479201 A.L.Matsuo, L.S.Silva, A.C.Torrecilhas, B.S.Pascoalino, T.C.Ramos, E.G.Rodrigues, S.Schenkman, A.C.Caires, and L.R.Travassos (2010).
In vitro and in vivo trypanocidal effects of the cyclopalladated compound 7a, a drug candidate for treatment of Chagas' disease.
  Antimicrob Agents Chemother, 54, 3318-3325.  
20093358 C.Juliana, T.Fernandes-Alnemri, J.Wu, P.Datta, L.Solorzano, J.W.Yu, R.Meng, A.A.Quong, E.Latz, C.P.Scott, and E.S.Alnemri (2010).
Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome.
  J Biol Chem, 285, 9792-9802.  
20485483 J.D.Durrant, H.Keränen, B.A.Wilson, and J.A.McCammon (2010).
Computational identification of uncharacterized cruzain binding sites.
  PLoS Negl Trop Dis, 4, e676.  
20527952 J.D.Durrant, M.D.Urbaniak, M.A.Ferguson, and J.A.McCammon (2010).
Computer-aided identification of Trypanosoma brucei uridine diphosphate galactose 4'-epimerase inhibitors: toward the development of novel therapies for African sleeping sickness.
  J Med Chem, 53, 5025-5032.  
20088534 K.Brak, I.D.Kerr, K.T.Barrett, N.Fuchi, M.Debnath, K.Ang, J.C.Engel, J.H.McKerrow, P.S.Doyle, L.S.Brinen, and J.A.Ellman (2010).
Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy.
  J Med Chem, 53, 1763-1773.
PDB code: 3iut
  20856868 Y.T.Chen, L.S.Brinen, I.D.Kerr, E.Hansell, P.S.Doyle, J.H.McKerrow, and W.R.Roush (2010).
In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi.
  PLoS Negl Trop Dis, 4, 0.
PDB code: 3lxs
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.

 

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