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PDBsum entry 3bpm
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protein ligands Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
3bpm

 

 

 

 

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Contents
Protein chains
243 a.a. *
Ligands
ACE-LEU-LEU-AR7 ×2
SO4 ×5
Waters ×76
* Residue conservation analysis
PDB id:
3bpm
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of falcipain-3 with its inhibitor, leupeptin
Structure: Cysteine protease falcipain-3. Chain: a, b. Leupeptin. Chain: d, c. Engineered: yes
Source: Plasmodium falciparum. Organism_taxid: 5833. Synthetic: yes. Streptomyces roseus. Organism_taxid: 66430
Resolution:
2.50Å     R-factor:   0.191     R-free:   0.224
Authors: I.D.Kerr,J.H.Lee,L.S.Brinen
Key ref: I.D.Kerr et al. (2009). Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity. J Med Chem, 52, 852-857. PubMed id: 19128015
Date:
18-Dec-07     Release date:   30-Dec-08    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8IIL0  (Q8IIL0_PLAF7) -  Falcipain-3 from Plasmodium falciparum (isolate 3D7)
Seq:
Struc: 		492 a.a.
243 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.22.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
J Med Chem 52:852-857 (2009)
PubMed id: 19128015  
 
 
Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.
I.D.Kerr, J.H.Lee, K.C.Pandey, A.Harrison, M.Sajid, P.J.Rosenthal, L.S.Brinen.
 
  ABSTRACT  
 
Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21420760 R.Ettari, M.Zappalà, N.Micale, G.Grazioso, S.Giofrè, T.Schirmeister, and S.Grasso (2011).
Peptidomimetics containing a vinyl ketone warhead as falcipain-2 inhibitors.
  Eur J Med Chem, 46, 2058-2065.  
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.  
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
19663681 K.Xiao, F.Jehle, C.Peters, T.Reinheckel, R.H.Schirmer, and T.Dandekar (2009).
CA/C1 peptidases of the malaria parasites Plasmodium falciparum and P. berghei and their mammalian hosts--a bioinformatical analysis.
  Biol Chem, 390, 1185-1197.  
19357776 S.Subramanian, M.Hardt, Y.Choe, R.K.Niles, E.B.Johansen, J.Legac, J.Gut, I.D.Kerr, C.S.Craik, and P.J.Rosenthal (2009).
Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3.
  PLoS ONE, 4, e5156.  
19834482 T.N.Wells, P.L.Alonso, and W.E.Gutteridge (2009).
New medicines to improve control and contribute to the eradication of malaria.
  Nat Rev Drug Discov, 8, 879-891.  
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.

 

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