title: Towards a systematic analysis of human short-chain dehydrogenases/reductases (SDR): Ligand identification and structure-activity relationships.
abstract: 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.
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Chitra
authors.initials: C
authors.lastname: Bhatia
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Oerum
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK; Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
authors.forename: James
authors.initials: J
authors.lastname: Bray
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Kavanagh
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Naeem
authors.initials: N
authors.lastname: Shafqat
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Yue
authors.affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK; Botnar Research Center, NIHR Oxford Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK. Electronic address: udo.oppermann@sgc.ox.ac.uk.
authors.forename: Udo
authors.initials: U
authors.lastname: Oppermann
mesh_terms: D064429:Fatty Acid Synthases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D008024:Ligands; D010088:Oxidoreductases; C036543:short chain trans-2-enoyl-CoA reductase; D009247:NADH, NADPH Oxidoreductases; D064429:Fatty Acid Synthases
keywords: Chemical biology; Differential scanning fluorimetry; Metabolism; Short-chain dehydrogenase/reductase; Structural genomics