2E99

E. coli undecaprenyl pyrophosphate synthase in complex with BPH-608


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.191 

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This is version 1.3 of the entry. See complete history


Literature

Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases

Guo, R.T.Cao, R.Liang, P.H.Ko, T.P.Chang, T.H.Hudock, M.P.Jeng, W.Y.Chen, C.K.M.Zhang, Y.Song, Y.Kuo, C.J.Yin, F.Oldfield, E.Wang, A.H.J.

(2007) Proc Natl Acad Sci U S A 104: 10022-10027

  • DOI: https://doi.org/10.1073/pnas.0702254104
  • Primary Citation of Related Structures:  
    2E8T, 2E8U, 2E8V, 2E8W, 2E8X, 2E90, 2E91, 2E92, 2E93, 2E94, 2E95, 2E98, 2E99, 2E9A, 2E9C, 2E9D

  • PubMed Abstract: 

    Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Here, we show that some bisphosphonates can also inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for antibacterial therapy. Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. In UPPS, there are a total of four binding sites (in five structures). These results are of general interest because they provide the first structures of GGPPS- and UPPS-inhibitor complexes, potentially important drug targets, in addition to revealing a remarkably broad spectrum of binding modes not seen in FPPS inhibition.


  • Organizational Affiliation

    Taiwan International Graduate Program, Institute of Biological Chemistry, Core Facility for Protein Crystallography, Academia Sinica, Taipei 115, Taiwan.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Undecaprenyl pyrophosphate synthetase
A, B
253Escherichia coliMutation(s): 0 
EC: 2.5.1.31
UniProt
Find proteins for P60472 (Escherichia coli (strain K12))
Explore P60472 
Go to UniProtKB:  P60472
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP60472
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.292α = 90
b = 68.156β = 90
c = 109.906γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-06-12
    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: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description