1QNH

Plasmodium falciparum Cyclophilin (double mutant) complexed with Cyclosporin A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.170 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The Three-Dimensional Structure of a Plasmodium Falciparum Cyclophilin in Complex with the Potent Anti-Malarial Cyclosporin A

Peterson, M.R.Hall, D.R.Berriman, M.Leonard, G.A.Fairlamb, A.H.Hunter, W.N.

(2000) J Mol Biol 298: 123

  • DOI: https://doi.org/10.1006/jmbi.2000.3633
  • Primary Citation of Related Structures:  
    1QNG, 1QNH

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Biochemistry The Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEPTIDYL-PROLYL CIS-TRANS ISOMERASE
A, B
170Plasmodium falciparumMutation(s): 2 
EC: 5.2.1.8
UniProt
Find proteins for Q25756 (Plasmodium falciparum)
Explore Q25756 
Go to UniProtKB:  Q25756
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ25756
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
CYCLOSPORIN A
C, D
11Tolypocladium inflatumMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  5 Unique
IDChains TypeFormula2D DiagramParent
ABA
Query on ABA
C, D
L-PEPTIDE LINKINGC4 H9 N O2ALA
BMT
Query on BMT
C, D
L-PEPTIDE LINKINGC10 H19 N O3THR
MLE
Query on MLE
C, D
L-PEPTIDE LINKINGC7 H15 N O2LEU
MVA
Query on MVA
C, D
L-PEPTIDE LINKINGC6 H13 N O2VAL
SAR
Query on SAR
C, D
PEPTIDE LINKINGC3 H7 N O2GLY
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.210 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.170 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.11α = 90
b = 115.12β = 90
c = 39.02γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-10-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Structure summary, Version format compliance
  • Version 1.2: 2012-11-30
    Changes: Other
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description