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PDBsum entry 3hd3
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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
3hd3

 

 

 

 

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Contents
Protein chains
215 a.a. *
Ligands
25B ×2
EDO ×2
EOH
PEG ×2
SO4
Waters ×395
* Residue conservation analysis
PDB id:
3hd3
Name: Hydrolase
Title: High resolution crystal structure of cruzain bound to the vinyl sulfone inhibitor smdc-256047
Structure: Cruzipain. Chain: a, b. Fragment: cruzain mature domain. Synonym: cruzaine, major cysteine proteinase. Engineered: yes. Mutation: yes
Source: Trypanosoma cruzi. Organism_taxid: 5693. Gene: cruzain. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
Resolution:
1.75Å     R-factor:   0.145     R-free:   0.176
Authors: I.D.Kerr,M.Debnath,L.S.Brinen
Key ref: C.Bryant et al. (2009). Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases. Bioorg Med Chem Lett, 19, 6218-6221. PubMed id: 19773167
Date:
06-May-09     Release date:   06-Oct-09    
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
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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

 

 
Bioorg Med Chem Lett 19:6218-6221 (2009)
PubMed id: 19773167  
 
 
Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases.
C.Bryant, I.D.Kerr, M.Debnath, K.K.Ang, J.Ratnam, R.S.Ferreira, P.Jaishankar, D.Zhao, M.R.Arkin, J.H.McKerrow, L.S.Brinen, A.R.Renslo.
 
  ABSTRACT  
 
We describe here the identification of non-peptidic vinylsulfones that inhibit parasite cysteine proteases in vitro and inhibit the growth of Trypanosoma brucei brucei parasites in culture. A high resolution (1.75 A) co-crystal structure of 8a bound to cruzain reveals how the non-peptidic P2/P3 moiety in such analogs bind the S2 and S3 subsites of the protease, effectively recapitulating important binding interactions present in more traditional peptide-based protease inhibitors and natural substrates.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20544024 I.D.Kerr, P.Wu, R.Marion-Tsukamaki, Z.B.Mackey, and L.S.Brinen (2010).
Crystal Structures of TbCatB and rhodesain, potential chemotherapeutic targets and major cysteine proteases of Trypanosoma brucei.
  PLoS Negl Trop Dis, 4, e701.
PDB code: 3hhi
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
20540517 R.S.Ferreira, A.Simeonov, A.Jadhav, O.Eidam, B.T.Mott, M.J.Keiser, J.H.McKerrow, D.J.Maloney, J.J.Irwin, and B.K.Shoichet (2010).
Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.
  J Med Chem, 53, 4891-4905.
PDB code: 3kku
  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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