1X83

Y104F IPP isomerase reacted with (S)-bromohydrine of IPP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.228 

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This is version 1.3 of the entry. See complete history


Literature

A Crystallographic Investigation of Phosphoantigen Binding to Isopentenyl Pyrophosphate/Dimethylallyl Pyrophosphate Isomerase

Wouters, J.Yin, F.Song, Y.Zhang, Y.Oudjama, Y.Stalon, V.Droogmans, L.Morita, C.T.Oldfield, E.

(2005) J Am Chem Soc 127: 536-537

  • DOI: https://doi.org/10.1021/ja040207i
  • Primary Citation of Related Structures:  
    1PPV, 1PPW, 1X83, 1X84

  • PubMed Abstract: 

    We report the crystallographic structures of the potent phosphoantigens Phosphostim (the bromohydrin of isopentenyl pyrophosphate) and E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate bound to the mevalonate pathway enzyme isopentenyl pyrophosphate/dimethylallyl pyrophosphate isomerase (IPPI). Racemic Phosphostim forms covalent complexes with IPPI: a 4-thioether with C67 and a 4-ester with E116. Only the E116 ester forms with the chiral species, S-Phosphostim, with the w.t. enzyme, while the C67 thioether forms with a mutant Y104F IPPI. The potent phosphoantigen HMBPP also binds to IPPI, but is only a weak ( approximately 50 muM) inhibitor. These results strongly support an SN2 reaction for inhibition of IPPI by Phosphostim, in contrast to the SN1 or concerted type of reaction found with epoxide inhibitors, which react at C-3, and are of general interest in the context of the development of novel mevalonate pathway inhibitors. They also provide clues as to the nature of the binding site of synthetic phosphoantigens in gammadelta T cell activation. In particular, both bromohydrin and epoxy phosphoantigens are potent, irreversible inhibitors of IPPI while HMBPP is only a weak inhibitor, ruling out an IPPI or IPPI-like target for HMBPP in gammadelta T cell activation.


  • Organizational Affiliation

    Institute de Recherche Wiame and Laboratoire de Microbiologie, Universite Libre de Bruxelles, 1 Avenue E. Gryson, 1070 Bruxelles, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isopentenyl-diphosphate delta-isomerase
A, B
189Escherichia coliMutation(s): 1 
Gene Names: idi
EC: 5.3.3.2
UniProt
Find proteins for Q46822 (Escherichia coli (strain K12))
Explore Q46822 
Go to UniProtKB:  Q46822
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ46822
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.228 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.09α = 90
b = 71.88β = 90
c = 91.73γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
XTALVIEWrefinement
SHELXL-97refinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-01-25
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations