6N7Z

Crystal structure of human FPPS in complex with an allosteric inhibitor YF-02037


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Chirality-Driven Mode of Binding of alpha-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS).

Feng, Y.Park, J.Li, S.G.Boutin, R.Viereck, P.Schilling, M.A.Berghuis, A.M.Tsantrizos, Y.S.

(2019) J Med Chem 62: 9691-9702

  • DOI: https://doi.org/10.1021/acs.jmedchem.9b01104
  • Primary Citation of Related Structures:  
    6N7Y, 6N7Z, 6N82, 6N83, 6OAG, 6OAH

  • PubMed Abstract: 

    Thienopyrimidine-based allosteric inhibitors of the human farnesyl pyrophosphate synthase (hFPPS), characterized by a chiral α-aminophosphonic acid moiety, were synthesized as enantiomerically enriched pairs, and their binding mode was investigated by X-ray crystallography. A general consensus in the binding orientation of all ( R )- and ( S )-enantiomers was revealed. This finding is a prerequisite for establishing a reliable structure-activity relationship (SAR) model.


  • Organizational Affiliation

    Department of Chemistry , McGill University , 801 Sherbrooke Street West , Montreal , Quebec H3A 0B8 , Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Farnesyl pyrophosphate synthaseA [auth F]375Homo sapiensMutation(s): 0 
Gene Names: FDPSFPSKIAA1293
EC: 2.5.1.10 (PDB Primary Data), 2.5.1.1 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P14324 (Homo sapiens)
Explore P14324 
Go to UniProtKB:  P14324
PHAROS:  P14324
GTEx:  ENSG00000160752 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP14324
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.234 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.862α = 90
b = 110.862β = 90
c = 75.038γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PROTEUM PLUSdata reduction
PROTEUM PLUSdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-11-06
    Type: Initial release
  • Version 1.1: 2019-11-27
    Changes: Database references
  • Version 1.2: 2023-10-11
    Changes: Data collection, Database references, Refinement description