2XWN

Crystal structure of IspD from Mycobacterium tuberculosis in complex with CTP and Mg


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 

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This is version 1.3 of the entry. See complete history


Literature

Structural and Functional Studies on Mycobacterial Ispd Enzymes

Bjorkelid, C.Bergfors, T.Henriksson, L.M.Stern, A.L.Unge, T.Mowbray, S.L.Jones, T.A.

(2011) Acta Crystallogr D Biol Crystallogr 67: 403

  • DOI: https://doi.org/10.1107/S0907444911006160
  • Primary Citation of Related Structures:  
    2XWL, 2XWM, 2XWN

  • PubMed Abstract: 

    A number of pathogens, including the causative agents of tuberculosis and malaria, synthesize isopentenyl diphosphate via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway rather than the classical mevalonate pathway found in humans. As part of a structure-based drug-discovery program against tuberculosis, IspD, the enzyme that carries out the third step in the MEP pathway, was targeted. Constructs of both the Mycobacterium smegmatis and the Mycobacterium tuberculosis enzymes that were suitable for structural and inhibitor-screening studies were engineered. Two crystal structures of the M. smegmatis enzyme were produced, one in complex with CTP and the other in complex with CMP. In addition, the M. tuberculosis enzyme was crystallized in complex with CTP. Here, the structure determination and crystallographic refinement of these crystal forms and the enzymatic characterization of the M. tuberculosis enzyme construct are reported. A comparison with known IspD structures allowed the definition of the structurally conserved core of the enzyme. It indicates potential flexibility in the enzyme and in particular in areas close to the active site. These well behaved constructs provide tools for future target-based screening of potential inhibitors. The conserved nature of the extended active site suggests that any new inhibitor will potentially exhibit broad-spectrum activity.


  • Organizational Affiliation

    Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-75124 Uppsala, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
2-C-METHYL-D-ERYTHRITOL 4-PHOSPHATE CYTIDYLYLTRANSFERASE
A, B
233Mycobacterium tuberculosis H37RvMutation(s): 0 
EC: 2.7.7.60
UniProt
Find proteins for P9WKG9 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WKG9 
Go to UniProtKB:  P9WKG9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WKG9
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.211 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.06α = 90
b = 82.25β = 90
c = 133.24γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-27
    Type: Initial release
  • Version 1.1: 2012-02-01
    Changes: Database references, Version format compliance
  • Version 1.2: 2019-03-06
    Changes: Data collection, Experimental preparation, Other
  • Version 1.3: 2019-05-15
    Changes: Data collection, Experimental preparation