3IHZ

Crystal structure of the FK506 binding domain of Plasmodium vivax FKBP35 in complex with FK506


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.67 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 

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This is version 1.2 of the entry. See complete history


Literature

NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35

Alag, R.Qureshi, I.A.Bharatham, N.Shin, J.Lescar, J.Yoon, H.S.

(2010) Protein Sci 19: 1577-1586

  • DOI: https://doi.org/10.1002/pro.438
  • Primary Citation of Related Structures:  
    3IHZ

  • PubMed Abstract: 

    The emergence of drug-resistant malaria parasites is the major threat to effective malaria control, prompting a search for novel compounds with mechanisms of action that are different from the traditionally used drugs. The immunosuppressive drug FK506 shows an antimalarial activity. The mechanism of the drug action involves the molecular interaction with the parasite target proteins PfFKBP35 and PvFKBP35, which are novel FK506 binding protein family (FKBP) members from Plasmodium falciparum and Plasmodium vivax, respectively. Currently, molecular mechanisms of the FKBP family proteins in the parasites still remain elusive. To understand their functions, here we have determined the structures of the FK506 binding domain of Plasmodium vivax (PvFKBD) in unliganded form by NMR spectroscopy and in complex with FK506 by X-ray crystallography. We found out that PvFKBP35 exhibits a canonical FKBD fold and shares kinetic profiles similar to those of PfFKBP35, the homologous protein in P. falciparum, indicating that the parasite FKBP family members play similar biological roles in their life cycles. Despite the similarity, differences were observed in the ligand binding modes between PvFKBD and HsFKBP12, a human FKBP homolog, which could provide insightful information into designing selective antimalarial drug against the parasites.


  • Organizational Affiliation

    Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
70 kDa peptidylprolyl isomerase, putative
A, B
126Plasmodium vivaxMutation(s): 0 
UniProt
Find proteins for A5K8X6 (Plasmodium vivax (strain Salvador I))
Explore A5K8X6 
Go to UniProtKB:  A5K8X6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA5K8X6
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FK5
Query on FK5

Download Ideal Coordinates CCD File 
C [auth A]8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN
C44 H69 N O12
QJJXYPPXXYFBGM-LFZNUXCKSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FK5 PDBBind:  3IHZ IC50: 160 (nM) from 1 assay(s)
Binding MOAD:  3IHZ IC50: 160 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.67 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.190 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.9α = 90
b = 40.9β = 109.5
c = 56.9γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
PHASERphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-06-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description