3NRR

Co-crystal structure of dihydrofolate reductase-thymidylate synthase from Babesia bovis with dUMP, Raltitrexed and NADP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis.

Begley, D.W.Edwards, T.E.Raymond, A.C.Smith, E.R.Hartley, R.C.Abendroth, J.Sankaran, B.Lorimer, D.D.Myler, P.J.Staker, B.L.Stewart, L.J.

(2011) Acta Crystallogr Sect F Struct Biol Cryst Commun 67: 1070-1077

  • DOI: https://doi.org/10.1107/S1744309111029009
  • Primary Citation of Related Structures:  
    3I3R, 3K2H, 3NRR

  • PubMed Abstract: 

    Babesiosis is a tick-borne disease caused by eukaryotic Babesia parasites which are morphologically similar to Plasmodium falciparum, the causative agent of malaria in humans. Like Plasmodium, different species of Babesia are tuned to infect different mammalian hosts, including rats, dogs, horses and cattle. Most species of Plasmodium and Babesia possess an essential bifunctional enzyme for nucleotide synthesis and folate metabolism: dihydrofolate reductase-thymidylate synthase. Although thymidylate synthase is highly conserved across organisms, the bifunctional form of this enzyme is relatively uncommon in nature. The structural characterization of dihydrofolate reductase-thymidylate synthase in Babesia bovis, the causative agent of babesiosis in livestock cattle, is reported here. The apo state is compared with structures that contain dUMP, NADP and two different antifolate inhibitors: pemetrexed and raltitrexed. The complexes reveal modes of binding similar to that seen in drug-resistant malaria strains and point to the utility of applying structural studies with proven cancer chemotherapies towards infectious disease research.


  • Organizational Affiliation

    Seattle Structural Genomics Center for Infectious Disease (http://www.ssgcid.org), USA. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dihydrofolate reductase-thymidylate synthase
A, B
515Babesia bovisMutation(s): 0 
Gene Names: BBOV_II000780
EC: 2.1.1.45
UniProt
Find proteins for A7ASX7 (Babesia bovis)
Explore A7ASX7 
Go to UniProtKB:  A7ASX7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA7ASX7
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
D [auth A],
T [auth B]
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
D16
Query on D16

Download Ideal Coordinates CCD File 
E [auth A],
G [auth A],
U [auth B],
W [auth B]
TOMUDEX
C21 H22 N4 O6 S
IVTVGDXNLFLDRM-HNNXBMFYSA-N
UMP
Query on UMP

Download Ideal Coordinates CCD File 
F [auth A],
V [auth B]
2'-DEOXYURIDINE 5'-MONOPHOSPHATE
C9 H13 N2 O8 P
JSRLJPSBLDHEIO-SHYZEUOFSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
R [auth B]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
GOL
Query on GOL

Download Ideal Coordinates CCD File 
O [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

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AA [auth B]
H [auth A]
I [auth A]
J [auth A]
K [auth A]
AA [auth B],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
P [auth A],
Q [auth B],
X [auth B],
Y [auth B],
Z [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A],
S [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.33α = 119.61
b = 83.83β = 102.04
c = 83.92γ = 90.26
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
PHASESphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-14
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-09-21
    Changes: Database references
  • Version 1.3: 2012-10-10
    Changes: Non-polymer description
  • Version 1.4: 2017-11-08
    Changes: Refinement description
  • Version 1.5: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description