Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: a novel, cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase.
|Abstract||Human DHRS6 is a previously uncharacterized member of the short chain dehydrogenases/reductase family and displays significant homologies to bacterial hydroxybutyrate dehydrogenases. Substrate screening reveals sole NAD(+)-dependent conversion of (R)-hydroxybutyrate to acetoacetate with K(m) values of about 10 mm, consistent with plasma levels of circulating ketone bodies in situations of starvation or ketoacidosis. The structure of human DHRS6 w ... [truncated at 450 characters in length]|
|Author||Guo, Kunde; Lukacik, Petra; Papagrigoriou, Evangelos; et al|
|Subject||Amino Acid Motifs Amino Acid Sequence Animals Arginine Binding Sites Cloning, Molecular Crystallography, X-Ray Cytosol Dose-Response Relationship, Drug Exons Green Fluorescent Proteins Hela Cells Humans Hydrogen-Ion Concentration Hydroxybutyrate Dehydrogenase Kinetics Lipids Mitochondria Models, Molecular Molecular Sequence Data Oxidoreductases Phylogeny Protein Conformation Protein Folding Protein Structure, Tertiary Sequence Homology, Amino Acid Substrate Specificity Sulfates chemistry enzymology metabolism metabolism chemistry genetics chemistry metabolism chemistry chemistry|
Evaluation of micro-parallel liquid chromatography as a method for HTS-coupled actives verification.
|Abstract||The identification of biologically active compounds from high-throughput screening (HTS) can involve considerable postscreening analysis to verify the nature of the sample activity. In this study we evaluated the performance of micro-parallel liquid chromatography (microPLC) as a separation-based enzyme assay platform for follow-up of compound activities found in quantitative HTS of two different targets, a hydrolase and an oxidoreductase. In an ... [truncated at 450 characters in length]|
|Author||Simeonov, Anton; Yasgar, Adam; Klumpp, Carleen; et al|
|Subject||Chromatography, Gas Chromatography, High Pressure Liquid Chromatography, Liquid Dose-Response Relationship, Drug Drug Evaluation, Preclinical Enzyme Activation False Positive Reactions Fluorometry Glucosylceramidase Hydroxymethylglutaryl CoA Reductases Indicators and Reagents Spectrometry, Fluorescence Spectrophotometry, Ultraviolet methods instrumentation methods drug effects analysis metabolism analysis metabolism|
Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases.
|Abstract||The dynamic methylation of histone lysyl residues plays an important role in biology by regulating transcription, maintaining genomic integrity, and by contributing to epigenetic effects. Here we describe a variety of inhibitor scaffolds that inhibit the human 2-oxoglutarate-dependent JMJD2 subfamily of histone demethylases. Combined with structural data, these chemical starting points will be useful to generate small-molecule probes to analyze t ... [truncated at 450 characters in length]|
|Author||Rose, Nathan R; Ng, Stanley S; Mecinović, Jasmin; et al|
|Subject||Crystallography, X-Ray Dose-Response Relationship, Drug Enzyme Inhibitors Humans Ketoglutaric Acids Models, Molecular Molecular Structure Oxidoreductases, N-Demethylating Protein Structure, Tertiary Stereoisomerism Structure-Activity Relationship pharmacology chemical synthesis chemistry pharmacology antagonists and inhibitors metabolism|