The centaurin gamma-1 GTPase-like domain functions as an NTPase.
|Abstract||Centaurins are a family of proteins that contain GTPase-activating protein domains, with the gamma family members containing in addition a GTPase-like domain. Centaurins reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. In the present study, using X-ray structural analysis, enzymatic assays and nucleotide-binding studies, we show that, for C ... [truncated at 450 characters in length]|
|Author||Soundararajan, Meera; Yang, Xiaowen; Elkins, Jonathan M; et al|
|Subject||Amino Acid Sequence Binding Sites Cloning, Molecular Escherichia coli GTP-Binding Proteins GTPase-Activating Proteins Hydrolysis Models, Molecular Molecular Structure Nucleoside-Triphosphatase Nucleotides Protein Structure, Tertiary Signal Transduction Substrate Specificity ras Proteins metabolism chemistry metabolism chemistry metabolism chemistry metabolism metabolism chemistry metabolism|
Dynamic protein methylation in chromatin biology.
|Abstract||Post-translational modification of chromatin is emerging as an increasingly important regulator of chromosomal processes. In particular, histone lysine and arginine methylation play important roles in regulating transcription, maintaining genomic integrity, and contributing to epigenetic memory. Recently, the use of new approaches to analyse histone methylation, the generation of genetic model systems, and the ability to interrogate genome wide h ... [truncated at 450 characters in length]|
|Author||Ng, S S; Yue, W W; Oppermann, U; et al|
|Subject||Animals Arginine Chromatin DNA Damage Embryonic Stem Cells Epigenesis, Genetic Gene Expression Regulation Germ Cells Histone-Lysine N-Methyltransferase Histones Lysine Methylation Models, Molecular Molecular Structure Neoplasms Oxidoreductases, N-Demethylating Protein Conformation Protein Methyltransferases Protein Processing, Post-Translational Tumor Suppressor Protein p53 metabolism metabolism physiology physiology genetics metabolism metabolism genetics metabolism genetics metabolism chemistry genetics metabolism genetics metabolism|
Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
|Abstract||The nitrogen-containing bisphosphonates (N-BPs) are the main drugs currently used to treat diseases characterized by excessive bone resorption. The major molecular target of N-BPs is farnesylpyrophosphate synthase. N-BPs inhibit the enzyme by a mechanism that involves time dependent isomerization of the enzyme. We investigated features of N-BPs that confer maximal slow and tight-binding by quantifying the initial and final K(i)s and calculating t ... [truncated at 450 characters in length]|
|Author||Dunford, James E; Kwaasi, Aaron A; Rogers, Michael J; et al|
|Subject||Binding Sites Diphosphonates Enzyme Inhibitors Geranyltranstransferase Humans Models, Molecular Molecular Structure Nitrogen Stereoisomerism Structure-Activity Relationship Time Factors chemistry pharmacology chemistry pharmacology antagonists and inhibitors 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|
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|