A5044635110- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Microtubule and mitosis dynamics
- Light effects on plants
- Biochemical Analysis and Sensing Techniques
- Photosynthetic Processes and Mechanisms
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Photoreceptor and optogenetics research
- Ubiquitin and proteasome pathways
- Redox biology and oxidative stress
- Pneumocystis jirovecii pneumonia detection and treatment
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- Renin-Angiotensin System Studies
- Chemical Synthesis and Analysis
- Synthesis and Catalytic Reactions
- Regulation of Appetite and Obesity
- Metalloenzymes and iron-sulfur proteins
Charité - Universitätsmedizin Berlin
2016-2022
Humboldt-Universität zu Berlin
2018-2021
Freie Universität Berlin
2019-2021
Bayer (Germany)
2016
Abstract The melanocortin-4 receptor (MC4R), a hypothalamic master regulator of energy homeostasis and appetite, is class A G-protein-coupled prime target for the pharmacological treatment obesity. Here, we present cryo-electron microscopy structures MC4R–Gs-protein complexes with two drugs recently approved by FDA, peptide agonists NDP-α-MSH setmelanotide, 2.9 Å 2.6 resolution. Together signaling data from structure-derived MC4R mutants, complex reveal agonist-induced origin transmembrane...
Abstract Phytochromes are modular photoreceptors of plants, bacteria and fungi that use light as a source information to regulate fundamental physiological processes. Interconversion between the active inactive states is accomplished by photoinduced reaction sequence which couples sensor with output module. However, underlying molecular mechanism yet not fully understood due lack structural data functionally relevant intermediate states. Here we report crystal structure Meta-F state an Agp2...
Roniciclib (BAY 1000394) is a type I pan-CDK (cyclin-dependent kinase) inhibitor which has revealed potent efficacy in xenograft cancer models. Here, we show that roniciclib displays prolonged residence times on CDK2 and CDK9, whereas other CDKs are transient, thus giving rise to kinetic selectivity of roniciclib. Surprisingly, variation the substituent at 5-position pyrimidine scaffold results changes up 3 orders magnitude drug–target time. X-ray cocrystal structures have DFG-loop adaption...
The melanocortin-4 receptor (MC4R) can be endogenously activated by binding of melanocyte-stimulating hormones (MSH), which mediates anorexigenic effects. In contrast, the agouti-related peptide (AgRP) acts as an endogenous inverse agonist and suppresses ligand-independent basal signaling activity (orexigenic effects). Binding ligands to MC4R leads activation different G-protein subtypes or arrestin concomitant pathways. This is a key protein in hypothalamic regulation food intake energy...
Abstract PhrB from Agrobacterium fabrum is the first prokaryotic photolyase which repairs (6‐4) UV DNA photoproducts. The protein harbors three cofactors: enzymatically active FAD chromophore, a second 6,7‐dimethyl‐8‐ribityllumazine ( DMRL ) and cubane‐type Fe‐S cluster. Tyr424 of part ‐binding site could provide an electron link to Phr B Y 424F mutant showed reduced binding lesion loss repair. I 51W characterized by photoreduction repair capacity. We have determined crystal structures both...
SUMMARY The melanocortin-4 receptor (MC4R), a hypothalamic master regulator of energy homeostasis and appetite, is G-protein coupled prime target for the treatment obesity. Here, we present cryo-electron microscopy structures MC4R− Gs-protein complexes with two recently FDA-approved drugs, peptide agonists NDP-α-MSH setmelanotide, 2.9 Å 2.6 resolution. Together signaling data, complex reveal agonist-induced origin transmembrane helix (TM) 6 regulated activation. In both structures, different...