1Q0Q

Crystal structure of DXR in complex with the substrate 1-deoxy-D-xylulose-5-phosphate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.177 

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This is version 1.4 of the entry. See complete history


Literature

The crystal structure of E.coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation.

Mac Sweeney, A.Lange, R.Fernandes, R.P.Schulz, H.Dale, G.E.Douangamath, A.Proteau, P.J.Oefner, C.

(2005) J Mol Biol 345: 115-127

  • DOI: https://doi.org/10.1016/j.jmb.2004.10.030
  • Primary Citation of Related Structures:  
    1Q0H, 1Q0L, 1Q0Q

  • PubMed Abstract: 

    The key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) has been shown to be the target enzyme of fosmidomycin, an antimalarial, antibacterial and herbicidal compound. Here we report the crystal structure of selenomethionine-labelled Escherichia coli DXR in a ternary complex with NADPH and fosmidomycin at 2.2 A resolution. The structure reveals a considerable conformational rearrangement upon fosmidomycin binding and provides insights into the slow, tight binding inhibition mode of the inhibitor. Although the inhibitor displays an unusual non-metal mediated mode of inhibition, which is an artefact most likely due to the low metal affinity of DXR at the pH used for crystallization, the structural data add valuable information for the rational design of novel DXR inhibitors. Using this structure together with the published structural data and the 1.9 A crystal structure of DXR in a ternary complex with NADPH and the substrate 1-deoxy-D-xylulose 5-phosphate, a model for the physiologically relevant tight-binding mode of inhibition is proposed. The structure of the substrate complex must be interpreted with caution due to the presence of a second diastereomer in the active site.


  • Organizational Affiliation

    Morphochem AG, WRO-1055/338, Schwarzwaldallee 215, CH-4058, Basel, Switzerland.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
1-deoxy-D-xylulose 5-phosphate reductoisomerase
A, B
406Escherichia coliMutation(s): 0 
Gene Names: DXR
EC: 1.1.1.267
UniProt
Find proteins for P45568 (Escherichia coli (strain K12))
Explore P45568 
Go to UniProtKB:  P45568
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP45568
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.177 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.057α = 90
b = 122.846β = 90
c = 128.553γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
REFMACrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-07-20
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-10-03
    Changes: Advisory, Data collection
  • Version 1.4: 2023-08-16
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description