3RX2

Crystal Structure of Human Aldose Reductase Complexed with Sulindac Sulfone

Summary for 3RX2

• Entry DOI: 10.2210/pdb3rx2/pdb
• Related: 3RX3 3RX4
• Descriptor: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-[(3Z)-6-fluoranyl-2-methyl-3-[(4-methylsulfonylphenyl)methylidene]inden-1-yl]ethanoic acid, ... (4 entities in total)
• Functional Keywords: aldose reductase, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 39185.51

Authors

Zheng, X.,Chen, J.,Luo, H.,Hu, X. (deposition date: 2011-05-10, release date: 2011-11-30, Last modification date: 2023-11-01)

Primary citation

Zheng, X.,Zhang, L.,Zhai, J.,Chen, Y.,Luo, H.,Hu, X.
The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase
Febs Lett., 586:55-59, 2012

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.

PubMed: 22155003
DOI: 10.1016/j.febslet.2011.11.023

Experimental method

X-RAY DIFFRACTION (1.9 Å)