Structure and function of human 17beta-hydroxysteroid dehydrogenases.
|Abstract||17Beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the NAD(P)(H) dependent oxidoreduction at C17 oxo/beta-hydroxyl groups of androgen and estrogen hormones. This reversible reaction constitutes an important pre-receptor control mechanism for nuclear receptor ligands, since the conversion "switches" between the 17beta-OH receptor ligands and their inactive 17-oxo metabolites. At present, 14 mammalian 17beta-HSDs are described, of which at ... [truncated at 450 characters in length]|
|Author||Lukacik, Petra; Kavanagh, Kathryn L; Oppermann, Udo;|
|Subject||17-Hydroxysteroid Dehydrogenases Humans Protein Conformation Substrate Specificity chemistry drug effects physiology|
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|
Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs.
|Abstract||p21-activated kinases have been classified into two groups based on their domain architecture. Group II PAKs (PAK4-6) regulate a wide variety of cellular functions, and PAK deregulation has been linked to tumor development. Structural comparison of five high-resolution structures comprising all active, monophosphorylated group II catalytic domains revealed a surprising degree of domain plasticity, including a number of catalytically productive an ... [truncated at 450 characters in length]|
|Author||Eswaran, Jeyanthy; Lee, Wen Hwa; Debreczeni, Judit E; et al|
|Subject||Amino Acid Sequence Animals Catalytic Domain Crystallography Molecular Sequence Data Protein Conformation Protein Kinase Inhibitors Protein-Serine-Threonine Kinases Purines drug effects genetics chemistry pharmacology antagonists and inhibitors chemistry genetics chemistry|
Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis.
|Abstract||Cryptosporidiosis is a neglected disease without a wholly effective drug. We present a study demonstrating nitrogen-containing bisphosphonates (N-BPs) to be capable of inhibiting Cryptosporidium parvum at low micromolar concentrations in infected MDCK cells. Predictably, the mechanism of action is based on inhibition of biosynthesis of isoprenoids but the target enzyme is unexpectedly a distinctive C. parvum enzyme dubbed nonspecific polyprenyl p ... [truncated at 450 characters in length]|
|Author||Artz, Jennifer D; Dunford, James E; Arrowood, Michael J; et al|
|Subject||Animals Anti-Infective Agents Cattle Cells, Cultured Chromatography, Liquid Cryptosporidiosis Cryptosporidium parvum Crystallography, X-Ray Dimethylallyltranstransferase Diphosphonates Fluorescent Antibody Technique Humans Inhibitory Concentration 50 Models, Molecular Molecular Structure Protein Prenylation therapeutic use drug therapy drug effects enzymology antagonists and inhibitors metabolism pharmacology therapeutic use|
RhoB can adopt a Mg2+ free conformation prior to GEF binding.
|Author||Soundararajan, Meera; Turnbull, Andrew; Fedorov, Oleg; et al|
|Subject||Enzyme Stability Guanine Nucleotide Exchange Factors Hydrolysis Magnesium Models, Molecular Protein Binding Protein Structure, Secondary rhoA GTP-Binding Protein rhoB GTP-Binding Protein drug effects metabolism drug effects metabolism pharmacology drug effects chemistry chemistry metabolism|