PDBsum entry 2vn1

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Isomerase PDB id
Protein chains
123 a.a. *
FK5 ×2
Waters ×162
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Crystal structure of the fk506-binding domain of plasmodium falciparum fkbp35 in complex with fk506
Structure: 70 kda peptidylprolyl isomerase. Chain: a, b. Fragment: fk506-binding domain, residues 1-127. Synonym: plasmodium falciparum fkbp35. Engineered: yes
Source: Plasmodium falciparum. Organism_taxid: 36329. Strain: 3d7. Expressed in: escherichia coli. Expression_system_taxid: 469008.
2.35Å     R-factor:   0.194     R-free:   0.250
Authors: M.Kotaka,R.Alag,H.Ye,P.R.Preiser,H.S.Yoon,J.Lescar
Key ref: M.Kotaka et al. (2008). Crystal structure of the FK506 binding domain of Plasmodium falciparum FKBP35 in complex with FK506. Biochemistry, 47, 5951-5961. PubMed id: 18465874 DOI: 10.1021/bi800004u
30-Jan-08     Release date:   20-May-08    
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Protein chains
Pfam   ArchSchema ?
Q8I4V8  (Q8I4V8_PLAF7) -  FK506-binding protein (FKBP)-type peptidyl-propyl isomerase
304 a.a.
123 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Peptidylprolyl isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylproline (omega=180) = peptidylproline (omega=0)
Peptidylproline (omega=180)
= peptidylproline (omega=0)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein folding   1 term 


    Added reference    
DOI no: 10.1021/bi800004u Biochemistry 47:5951-5961 (2008)
PubMed id: 18465874  
Crystal structure of the FK506 binding domain of Plasmodium falciparum FKBP35 in complex with FK506.
M.Kotaka, H.Ye, R.Alag, G.Hu, Z.Bozdech, P.R.Preiser, H.S.Yoon, J.Lescar.
The emergence of multi-drug-resistant strains of Plasmodium parasites has prompted the search for alternative therapeutic strategies for combating malaria. One possible strategy is to exploit existing drugs as lead compounds. FK506 is currently used in the clinic for preventing transplant rejection. It binds to a alpha/beta protein module of approximately 120 amino acids known as the FK506 binding domain (FKBD), which is found in various organisms, including human, yeast, and Plasmodium falciparum (PfFKBD). Antiparasitic effects of FK506 and its analogues devoid of immunosuppressive activities have been demonstrated. We report here the crystallographic structure at 2.35 A resolution of PfFKBD complexed with FK506. Compared to the human FKBP12-FK506 complex reported earlier, the structure reveals structural differences in the beta5-beta6 segment that lines the FK506 binding site. The presence in PfFKBD of Cys-106 and Ser-109 (substituting for His-87 and Ile-90, respectively, in human FKBP12), which are 4-5 A from the nearest atom of the FK506 compound, suggests possible routes for the rational design of analogues of FK506 with specific antiparasitic activity. Upon ligand binding, several conformational changes occur in PfFKBD, including aromatic residues that shape the FK506 binding pocket as shown by NMR studies. A microarray analysis suggests that FK506 and cyclosporine A (CsA) might inhibit parasite development by interfering with the same signaling pathways.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20572013 R.Alag, I.A.Qureshi, N.Bharatham, J.Shin, J.Lescar, and H.S.Yoon (2010).
NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35.
  Protein Sci, 19, 1577-1586.
PDB code: 3ihz
19691130 R.Alag, N.Bharatham, A.Dong, T.Hills, A.Harikishore, A.A.Widjaja, S.G.Shochat, R.Hui, and H.S.Yoon (2009).
Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide.
  Protein Sci, 18, 2115-2124.
PDB code: 2fbn
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