Structural highlights
Function
ALDR_HUMAN Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Publication Abstract from PubMed
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 pi-pi 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.
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 FEBS Lett. 2012 Jan 2;586(1):55-9. Epub 2011 Dec 8. PMID:22155003[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. 2012 Jan 2;586(1):55-9. Epub 2011 Dec 8. PMID:22155003 doi:10.1016/j.febslet.2011.11.023
