Towards a systematic analysis of human short-chain dehydrogenases/reductases (SDR): Ligand identification and structure-activity relationships

Chem Biol Interact. 2015 Jun 5;234:114-25. doi: 10.1016/j.cbi.2014.12.013. Epub 2014 Dec 16.


Short-chain dehydrogenases/reductases (SDRs) constitute a large, functionally diverse branch of enzymes within the class of NAD(P)(H) dependent oxidoreductases. In humans, over 80 genes have been identified with distinct metabolic roles in carbohydrate, amino acid, lipid, retinoid and steroid hormone metabolism, frequently associated with inherited genetic defects. Besides metabolic functions, a subset of atypical SDR proteins appears to play critical roles in adapting to redox status or RNA processing, and thereby controlling metabolic pathways. Here we present an update on the human SDR superfamily and a ligand identification strategy using differential scanning fluorimetry (DSF) with a focused library of oxidoreductase and metabolic ligands to identify substrate classes and inhibitor chemotypes. This method is applicable to investigate structure-activity relationships of oxidoreductases and ultimately to better understand their physiological roles.

Keywords: Chemical biology; Differential scanning fluorimetry; Metabolism; Short-chain dehydrogenase/reductase; Structural genomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fatty Acid Synthases / genetics*
  • Fatty Acid Synthases / metabolism*
  • Humans
  • Ligands
  • NADH, NADPH Oxidoreductases / genetics*
  • NADH, NADPH Oxidoreductases / metabolism*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Phylogeny
  • Structure-Activity Relationship
  • Substrate Specificity / genetics


  • Ligands
  • Oxidoreductases
  • short chain trans-2-enoyl-CoA reductase
  • NADH, NADPH Oxidoreductases
  • Fatty Acid Synthases