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Single-Molecule Detection Reveals Different Roles of Skp and SurA as Chaperones
10.1021/acschembio.8b00097 2018-03-20 Skp and SurA are both periplasmic chaperones involved in the biogenesis of Escherichia coli β-barrel outer membrane proteins (OMPs). It is commonly assumed that SurA plays a major role whereas Skp is a minor factor. However, there is no molecular evidence for... |
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Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach
10.1021/acschembio.7b01093 2018-03-20 Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campai... |
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A High Content Screen in Macrophages Identifies Small Molecule Modulators of STING-IRF3 and NFkB Signaling
10.1021/acschembio.7b01060 2018-03-19 We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content s... |
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Targeting of G-Quadruplex Harboring Pre-miRNA 92b by LNA Rescues PTEN Expression in NSCL Cancer Cells
10.1021/acschembio.7b00749 2018-03-19 Since the elevated levels of microRNAs (miRNAs) often cause various diseases, selective inhibition of miRNA maturation is an important therapeutic strategy. Commonly used anti-miRNA strategies are limited to targeting of mature miRNAs, as the upstream targeti... |
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Photochemical Control of Protein Arginine Deiminase (PAD) Activity
10.1021/acschembio.8b00053 2018-03-16 Protein arginine deiminases (PADs) play an important role in the pathogenesis of various diseases, including rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis, and breast cancer. Therefore, the development of PAD inhibitors has drawn signifi... |
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DNA Polymerase θ Increases Mutational Rates in Mitochondrial DNA
10.1021/acschembio.8b00072 2018-03-15 Replication and maintenance of mitochondrial DNA (mtDNA) is essential for cellular function, yet few DNA polymerases are known to function in mitochondria. Here, we conclusively demonstrate that DNA polymerase θ (Polθ) localizes to mitochondria and explore wh... |
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Determinants of ligand subtype-selectivity at α1A-adrenoceptor revealed using Saturation Transfer Difference (STD) NMR
10.1021/acschembio.8b00191 2018-03-14 α1A- and α1B-adrenoceptors (α1A-AR and α1B-AR) are closely related G protein-coupled receptors (GPCRs) that modulate the cardiovascular and nervous systems in response to binding epinephrine and norepinephrine. The GPCR gene super-family is made up of numerou... |
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Acyl-CoA Oxidases Fine-Tune the Production of Ascaroside Pheromones with Specific Side Chain Lengths
10.1021/acschembio.7b01021 2018-03-14 Caenorhabditis elegans produces a complex mixture of ascaroside pheromones to control its development and behavior. Acyl-CoA oxidases, which participate in β-oxidation cycles that shorten the side chains of the ascarosides, regulate the mixture of pheromones ... |
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Functionally Biased D2R Antagonists: Targeting the β-Arrestin Pathway to Improve Antipsychotic Treatment
10.1021/acschembio.8b00168 2018-03-14 Schizophrenia is a severe neuropsychiatric disease that lacks completely effective and safe therapies. As a polygenic disorder, genetic studies have only started to shed light on its complex etiology. To date, the positive symptoms of schizophrenia are well-m... |
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Determination of the Subcellular Localization and Mechanism of Action of Ferrostatins in Suppressing Ferroptosis
10.1021/acschembio.8b00199 2018-03-13 Ferroptosis is a form of nonapoptotic cell death characterized by the unchecked accumulation of lipid peroxides. Ferrostatin-1 and its analogs (ferrostatins) specifically prevent ferroptosis in multiple contexts, but many aspects of their molecular mechanism ... |