2WBD

FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE-1- PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH AN AMP SITE INHIBITOR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Sulfonylureido Thiazoles as Fructose-1,6-Bisphosphatase Inhibitors for the Treatment of Type-2 Diabetes.

Kitas, E.Mohr, P.Kuhn, B.Wessel, H.P.Hebeisen, P.Haap, W.Ruf, A.Benz, J.Joseph, C.Huber, W.Alvarez Sanchez, R.Paehler, A.Bernadeau, A.Gubler, M.Schott, B.Tozzo, E.

(2010) Bioorg Med Chem Lett 20: 594

  • DOI: https://doi.org/10.1016/j.bmcl.2009.11.093
  • Primary Citation of Related Structures:  
    2WBB, 2WBD

  • PubMed Abstract: 

    Sulfonylureido thiazoles were identified from a HTS campaign and optimized through a combination of structure-activity studies, X-ray crystallography and molecular modeling to yield potent inhibitors of fructose-1,6-bisphosphatase. Compound 12 showed favorable ADME properties, for example, F=70%, and a robust 32% glucose reduction in the acute db/db mouse model for Type-2 diabetes.


  • Organizational Affiliation

    F. Hoffmann-La Roche Ltd, Discovery Research Basel, CH-4070 Basel, Switzerland. eric_a.kitas@roche.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FRUCTOSE-1,6-BISPHOSPHATASE 1
A, B, C, D, E
A, B, C, D, E, F, G, H
338Homo sapiensMutation(s): 0 
EC: 3.1.3.11
UniProt & NIH Common Fund Data Resources
Find proteins for P09467 (Homo sapiens)
Explore P09467 
Go to UniProtKB:  P09467
PHAROS:  P09467
GTEx:  ENSG00000165140 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09467
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
RO5 PDBBind:  2WBD IC50: 230 (nM) from 1 assay(s)
BindingDB:  2WBD IC50: min: 100, max: 230 (nM) from 2 assay(s)
EC50: 3.20e+4 (nM) from 1 assay(s)
Binding MOAD:  2WBD IC50: 230 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.842α = 90
b = 285.402β = 97.57
c = 83.552γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-12-22
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description