3RX2

Crystal Structure of Human Aldose Reductase Complexed with Sulindac Sulfone

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.141 
  • R-Value Observed: 0.143 

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

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

Zheng, X., Zhang, L., Zhai, J., Chen, Y., Luo, H., Hu, X.

(2012) FEBS Lett 586: 55-59

  • DOI: https://doi.org/10.1016/j.febslet.2011.11.023
  • Primary Citation of Related Structures:  
    3RX2, 3RX3, 3RX4, 3S3G

  • PubMed Abstract: 

    Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vitro. Crystallographic analysis reveals that π-π stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo.

    • Organizational Affiliation: 

    School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aldose reductase336Homo sapiensMutation(s): 0 
Gene Names: AKR1B1, ALDR1
EC: 1.1.1.21 (PDB Primary Data), 1.1.1.372 (UniProt), 1.1.1.300 (UniProt), 1.1.1.54 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P15121 (Homo sapiens)
Explore P15121 
Go to UniProtKB:  P15121
PHAROS:  P15121
GTEx:  ENSG00000085662 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15121
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP
Download Ideal Coordinates CCD File 
B [auth A]NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
SLO
Query on SLO
Download Ideal Coordinates CCD File 
C [auth A]2-[(3Z)-6-fluoranyl-2-methyl-3-[(4-methylsulfonylphenyl)methylidene]inden-1-yl]ethanoic acid
C20 H17 F O4 S
MVGSNCBCUWPVDA-MFOYZWKCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.141 
  • R-Value Observed: 0.143 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.187α = 90
b = 67.081β = 91.94
c = 49.357γ = 90
Software Package:
Software NamePurpose
CrysalisProdata collection
MOLREPphasing
PHENIXrefinement
CrysalisProdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-11-30
    Type: Initial release
  • Version 1.1: 2013-07-03
    Changes: Database references
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description