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PDBsum entry 3i79

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protein ligands links
Transferase PDB id
3i79
Jmol
Contents
Protein chain
455 a.a. *
Ligands
EDO
Waters ×75
* Residue conservation analysis
PDB id:
3i79
Name: Transferase
Title: Calcium-dependent protein kinase 1 from toxoplasma gondii (t
Structure: Calmodulin-domain protein kinase 1. Chain: a. Fragment: residues 30-507. Engineered: yes
Source: Toxoplasma gondii. Organism_taxid: 5811. Gene: cdpk1. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.04Å     R-factor:   0.215     R-free:   0.258
Authors: E.T.Larson,E.A.Merritt,Medical Structural Genomics Of Pathog Protozoa (Msgpp)
Key ref: K.K.Ojo et al. (2010). Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors. Nat Struct Mol Biol, 17, 602-607. PubMed id: 20436472
Date:
08-Jul-09     Release date:   11-Aug-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9BJF5  (Q9BJF5_TOXGO) -  Calmodulin-domain protein kinase 1
Seq:
Struc:
507 a.a.
455 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     phosphorylation   2 terms 
  Biochemical function     nucleotide binding     8 terms  

 

 
Nat Struct Mol Biol 17:602-607 (2010)
PubMed id: 20436472  
 
 
Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.
K.K.Ojo, E.T.Larson, K.R.Keyloun, L.J.Castaneda, A.E.Derocher, K.K.Inampudi, J.E.Kim, T.L.Arakaki, R.C.Murphy, L.Zhang, A.J.Napuli, D.J.Maly, C.L.Verlinde, F.S.Buckner, M.Parsons, W.G.Hol, E.A.Merritt, W.C.Van Voorhis.
 
  ABSTRACT  
 
New drugs are needed to treat toxoplasmosis. Toxoplasma gondii calcium-dependent protein kinases (TgCDPKs) are attractive targets because they are absent in mammals. We show that TgCDPK1 is inhibited by low nanomolar levels of bumped kinase inhibitors (BKIs), compounds inactive against mammalian kinases. Cocrystal structures of TgCDPK1 with BKIs confirm that the structural basis for selectivity is due to the unique glycine gatekeeper residue in the ATP-binding site. We show that BKIs interfere with an early step in T. gondii infection of human cells in culture. Furthermore, we show that TgCDPK1 is the in vivo target of BKIs because T. gondii expressing a glycine to methionine gatekeeper mutant enzyme show significantly decreased sensitivity to BKIs. Thus, design of selective TgCDPK1 inhibitors with low host toxicity may be achievable.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20442739 C.Doerig, and O.Billker (2010).
A parasite calcium switch and Achilles' heel revealed.
  Nat Struct Mol Biol, 17, 541-543.  
20580218 L.D.Sibley (2010).
How apicomplexan parasites move in and out of cells.
  Curr Opin Biotechnol, 21, 592-598.  
  20951971 R.Tewari, U.Straschil, A.Bateman, U.Böhme, I.Cherevach, P.Gong, A.Pain, and O.Billker (2010).
The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission.
  Cell Host Microbe, 8, 377-387.  
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.