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PDBsum entry 1me3
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Hydrolase PDB id
1me3

 

 

 

 

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Contents
Protein chain
215 a.a. *
Ligands
P10
Waters ×548
* Residue conservation analysis
PDB id:
1me3
Name: Hydrolase
Title: High resolution crystal structure analysis of cruzain non-covalently bound to a hydroxymethyl ketone inhibitor (ii)
Structure: Cruzipain. Chain: a. Fragment: catalytic domain. Synonym: major cysteine proteinase, cruzaine, cruzain. Engineered: yes
Source: Trypanosoma cruzi. Organism_taxid: 5693. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.20Å     R-factor:   0.105     R-free:   0.135
Authors: L.S.Brinen,L.Huang,J.A.Ellman
Key ref: L.Huang et al. (2003). Crystal structures of reversible ketone-Based inhibitors of the cysteine protease cruzain. Bioorg Med Chem Lett, 11, 21-29. PubMed id: 12467703 DOI: 10.1016/S0968-0896(02)00427-3
Date:
07-Aug-02     Release date:   18-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
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: 10.1016/S0968-0896(02)00427-3 Bioorg Med Chem Lett 11:21-29 (2003)
PubMed id: 12467703  
 
 
Crystal structures of reversible ketone-Based inhibitors of the cysteine protease cruzain.
L.Huang, L.S.Brinen, J.A.Ellman.
 
  ABSTRACT  
 
The crystal structures of two hydroxymethyl ketone inhibitors complexed to the cysteine protease cruzain have been determined at 1.1 and 1.2 A resolution, respectively. These high resolution crystal structures provide the first structures of non-covalent inhibitors bound to cruzain. A series of compounds were prepared and tested based upon the structures providing further insight into the key binding interactions.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19908842 B.T.Mott, R.S.Ferreira, A.Simeonov, A.Jadhav, K.K.Ang, W.Leister, M.Shen, J.T.Silveira, P.S.Doyle, M.R.Arkin, J.H.McKerrow, J.Inglese, C.P.Austin, C.J.Thomas, B.K.Shoichet, and D.J.Maloney (2010).
Identification and optimization of inhibitors of Trypanosomal cysteine proteases: cruzain, rhodesain, and TbCatB.
  J Med Chem, 53, 52-60.
PDB code: 3i06
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.  
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
20799311 K.Steert, M.Berg, J.C.Mottram, G.D.Westrop, G.H.Coombs, P.Cos, L.Maes, J.Joossens, P.Van der Veken, A.Haemers, and K.Augustyns (2010).
α-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB.
  ChemMedChem, 5, 1734-1748.  
  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
19620707 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, and L.S.Brinen (2009).
Vinyl sulfones as antiparasitic agents and a structural basis for drug design.
  J Biol Chem, 284, 25697-25703.
PDB codes: 2oz2 2p7u 3bwk
19143838 I.Redzynia, A.Ljunggren, A.Bujacz, M.Abrahamson, M.Jaskolski, and G.Bujacz (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.
PDB code: 3e1z
17298440 F.C.Reis, T.F.Costa, T.Sulea, A.Mezzetti, J.Scharfstein, D.Brömme, R.Ménard, and A.P.Lima (2007).
The propeptide of cruzipain--a potent selective inhibitor of the trypanosomal enzymes cruzipain and brucipain, and of the human enzyme cathepsin F.
  FEBS J, 274, 1224-1234.  
16777845 T.Hogg, K.Nagarajan, S.Herzberg, L.Chen, X.Shen, H.Jiang, M.Wecke, C.Blohmke, R.Hilgenfeld, and C.L.Schmidt (2006).
Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum.
  J Biol Chem, 281, 25425-25437.
PDB code: 2ghu
  16542015 A.Kennedy, A.Nelson, and A.Perry (2005).
Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives.
  Beilstein J Org Chem, 1, 2.  
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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