PDBsum entry 1qng

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Isomerase/immunosuppressant PDB id
Protein chains
170 a.a. *
11 a.a. *
Waters ×175
* Residue conservation analysis
PDB id:
Name: Isomerase/immunosuppressant
Title: Plasmodium falciparum cyclophilin complexed with cyclosporin a
Structure: Peptidyl-prolyl cis-trans isomerase. Chain: a. Synonym: ppiase, rotamase, cyclophilin a. Engineered: yes. Cyclosporin a. Chain: d. Synonym: cyclosporine, ciclosporin, ciclosporine
Source: Plasmodium falciparum. Organism_taxid: 5833. Expressed in: escherichia coli. Expression_system_taxid: 469008. Tolypocladium inflatum. Organism_taxid: 29910
Biol. unit: Dimer (from PQS)
2.10Å     R-factor:   0.150     R-free:   0.190
Authors: M.R.Peterson,D.R.Hall,W.N.Hunter
Key ref:
M.R.Peterson et al. (2000). The three-dimensional structure of a Plasmodium falciparum cyclophilin in complex with the potent anti-malarial cyclosporin A. J Mol Biol, 298, 123-133. PubMed id: 10756109 DOI: 10.1006/jmbi.2000.3633
14-Oct-99     Release date:   13-Oct-00    
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Protein chain
Pfam   ArchSchema ?
Q25756  (Q25756_PLAFA) -  Peptidyl-prolyl cis-trans isomerase
171 a.a.
170 a.a.
Protein chain
No UniProt id for this chain
Struc: 11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: 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   2 terms 
  Biochemical function     isomerase activity     2 terms  


    Added reference    
DOI no: 10.1006/jmbi.2000.3633 J Mol Biol 298:123-133 (2000)
PubMed id: 10756109  
The three-dimensional structure of a Plasmodium falciparum cyclophilin in complex with the potent anti-malarial cyclosporin A.
M.R.Peterson, D.R.Hall, M.Berriman, J.A.Nunes, G.A.Leonard, A.H.Fairlamb, W.N.Hunter.
Cyclosporin A (CsA) is a potent anti-malarial compound in vitro and in vivo in mice though better known for its immunosuppressive properties in humans. Crystal structures of wild-type and a double mutant Plasmodium falciparum cyclophilin (PfCyP19 and mPfCyP19) complexed with CsA have been determined using diffraction terms to a resolution of 2.1 A (1 A=0.1 nm). The wild-type has a single PfCyP19/CsA complex per asymmetric unit in space group P1 and refined to an R-work of 0.15 and R-free of 0.19. An altered cyclophilin, with two accidental mutations, Phe120 to Leu in the CsA binding pocket and Leu171 to Trp at the C terminus, presents two complexes per asymmetric unit in the orthorhombic space group P2(1)2(1)2. This refined to an R-work of 0.18 and R-free 0.21. The mutations were identified from the crystallographic analysis and the C-terminal alteration helps to explain the different crystal forms obtained. PfCyP19 shares approximately 61 % sequence identity with human cyclophilin A (hCyPA) and the structures are similar, consisting of an eight-stranded antiparallel beta-barrel core capped by two alpha-helices. The fold creates a hydrophobic active-site, the floor of which is formed by side-chains of residues from four antiparallel beta-strands and the walls from loops and turns. We identified C-H.O hydrogen bonds between the drug and protein that may be an important feature of cyclophilins and suggest a general mode of interaction between hydrophobic molecules. Comparisons with cyclophilin-dipeptide complexes suggests that a specific C-H.O hydrogen bonding interaction may contribute to ligand binding. Residues Ser106, His99 and Asp130, located close to the active site and conserved in most cyclophilins, are arranged in a manner reminiscent of a serine protease catalytic triad. A Ser106Ala mutant was engineered to test the hypothesis that this triad contributes to CyP function. Mutant and wild-type enzymes were found to have similar catalytic properties.
  Selected figure(s)  
Figure 2.
Figure 2. The PfCyP19/CsA complex. Protein is represented in ribbon form with secondary structure elements helices (red); C-terminal direction, for b-strands (yellow arrows), a section of 3[10] helix (cyan ribbon). The loop segments are numbered 1 to 5. CsA is illustrated as a stick model where carbon positions (black), nitrogen (blue), and oxygen (red). Figure 2, Figure 3, Figure 4, Figure 5 and Figure 6 inclusive were constructed using MOLSCRIPT [Kraulis 1991] and RASTER3D [Merritt and Bacon 1997].
Figure 6.
Figure 6. The difference in the active site between the native (stick model) and the mutant (ball and stick model) highlighting the Phe120Leu mutation in relation to MeVal11 of CsA.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 298, 123-133) copyright 2000.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17875391 P.Gayathri, H.Balaram, and M.R.Murthy (2007).
Structural biology of plasmodial proteins.
  Curr Opin Struct Biol, 17, 744-754.  
  17277440 V.Venugopal, B.Sen, A.K.Datta, and R.Banerjee (2007).
Structure of cyclophilin from Leishmania donovani at 1.97 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 60-64.
PDB code: 2haq
15735342 L.L.Huang, X.M.Zhao, C.Q.Huang, L.Yu, and Z.X.Xia (2005).
Structure of recombinant human cyclophilin J, a novel member of the cyclophilin family.
  Acta Crystallogr D Biol Crystallogr, 61, 316-321.
PDB code: 1xyh
15469936 F.Yarovinsky, J.F.Andersen, L.R.King, P.Caspar, J.Aliberti, H.Golding, and A.Sher (2004).
Structural determinants of the anti-HIV activity of a CCR5 antagonist derived from Toxoplasma gondii.
  J Biol Chem, 279, 53635-53642.  
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