A5061420654- Metal-Catalyzed Oxygenation Mechanisms
- Microbial bioremediation and biosurfactants
- Pharmacogenetics and Drug Metabolism
- Estrogen and related hormone effects
- Retinoids in leukemia and cellular processes
- Enzyme Structure and Function
- Redox biology and oxidative stress
- Psoriasis: Treatment and Pathogenesis
- Drug Transport and Resistance Mechanisms
- Polyamine Metabolism and Applications
- Inflammatory mediators and NSAID effects
- Metal complexes synthesis and properties
- Diabetes Management and Research
- Microbial metabolism and enzyme function
- Radiation Therapy and Dosimetry
- Pesticide and Herbicide Environmental Studies
- RNA and protein synthesis mechanisms
- Chemical Thermodynamics and Molecular Structure
- Toxic Organic Pollutants Impact
- Electron Spin Resonance Studies
- Photosynthetic Processes and Mechanisms
- Cholesterol and Lipid Metabolism
- Steroid Chemistry and Biochemistry
- Hemoglobin structure and function
- Biopolymer Synthesis and Applications
Karo Pharma (Sweden)
2003-2023
Abbott (Sweden)
2004
Swedish University of Agricultural Sciences
1995-2000
Umeå University
1996
Schools of Visual Arts, The Royal Danish Academy of Fine Arts
1996
Here we describe the three-dimensional crystal structures of human glucocorticoid receptor ligand-binding domain (GR-LBD) in complex with antagonist RU-486 at 2.3 Å resolution and agonist dexamethasone ligand together a coactivator peptide 2.8 Å. The structure was solved several different forms, two helix 12 intact (GR1 GR3) one protease-digested C terminus (GR2). In GR1, part is position that covers co-activator pocket, whereas GR3, swapping seen between crystallographically identical...
Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating levels, but systemic antagonism can produce adrenal insufficiency other undesirable side effects. These hepatic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked bile acid in an appropriate manner. Bile conjugation accomplished with minimal loss binding affinity for GR. The resultant conjugates remain potent cell-based functional...
The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist anticipated to reduce production IL-17, key proinflammatory cytokine. Through high-throughput screening approach, we identified molecule displaying binding affinity RORC2, inhibition IL-17 in Th17 cells, and selectivity against related RORA RORB isoforms. Lead optimization improve potency metabolic...
The expression of superoxide dismutase in all aerobic living organisms supports the concept that radicals are toxic species. However, because limited chemical reactivity superoxide, mechanisms this toxicity still uncertain. Protein R2, small component ribonucleotide reductase, a key enzyme for DNA synthesis, is shown here to be irreversibly inactivated during incubation with an enzymatic generator radicals, at neutral pH. During inactivation essential tyrosyl radical protein R2 destroyed....
Ribonucleotide reductase is a key enzyme for DNA synthesis. Its small component, named protein R2, contains tyrosyl radical essential activity. Consequently, scavengers are potential antiproliferative agents. In this study, we show that the reactivity of towards phenols, hydrazines, hydroxyurea, dithionite and ascorbate can be finely tuned by relatively modifications its hydrophobic close environment. For example, in pocket, Leu77→Phe mutation resulted with much higher susceptibility to...
Macrocyclic retinoic acid receptor-related orphan receptor C2 (RORC2) inverse agonists have been designed with favorable properties for topical administration. Inspired by the unanticipated bound conformation of an acyclic sulfonamide-based RORC2 ligand from cocrystal structure analysis, macrocyclic linker connections between halves molecule were explored. Further optimization analogues was accomplished to maximize potency and refine physiochemical (MW, lipophilicity) best suited...
The R2 protein component of mouse ribonucleotide reductase has been obtained from overproducing Escherichia coli bacteria. It crystallized using NaCl as precipitant. crystals are orthorhombic, space group C222 1 with cell dimensions and diffract to at least 2.5 Å. asymmetric unit the contains one monomer. Rotation translation function searches a model based on weakly homologous E. gave significant peak. about crystallographic 2‐fold axis parallel a‐axis produces an dimer interactions very...
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionLiver-Selective Glucocorticoid Antagonists: A Novel Treatment for Type 2 Diabetes.Thomas W. von Geldern, Noah Tu, Philip R. Kym, James T. Link, Hwan-Soo Jae, Chunqiu Lai, Theresa Apelqvist, Patrik Rhonnstad, Lars Hagberg, Konrad Koehler, Marlena Grynfarb, Annika Goos-Nilsson, Johnny Sandberg, Marie Österlund, Tomas Barkhem, Höglund, Jiahong Wang, Steven Fung, Denise Wilcox, Phong Nguyen, Clarissa...
Two trigonal crystal structures of naphthalene 1,2-dioxygenase from Pseudomonas sp. NCIB 9816-4 have been refined at 2.6 Å resolution. The space group is R3, with four heterodimers in the asymmetric unit. crystallographic threefold axis coincides symmetry active molecule, a mushroom-shaped α3β3 hexamer. formed by symmetrical contacts between hexamers on three different interaction surfaces, one β-subunit and other two α-subunits. Nickel ions mediate α-subunit interactions. types packing...
Nuclear receptors bind to DNA and activate in general the transcription of sets genes response binding cognate ligands, usually small lipophilic molecules such as steroids, vitamins, fatty acid derivatives.About 50 nuclear receptor have been identified human genome, but most them no known ligand are therefore called orphans; their biological functions also poorly understood.Among orphan receptors, some appear be constitutively active.We solved structure ligand-binding domain (LBD) two...