Showing papers in "Chemistry & Biology in 2009"

TL;DR: Mechanistic and structural studies confirm that PF-3845 is a covalent inhibitor that carbamylates FAAH's serine nucleophile, and designate PF- 3845 as a valuable pharmacological tool for in vivo characterization of the endocannabinoid system.

TL;DR: A general small molecule inhibitor of formin homology 2 domains (SMIFH2) is identified by screening compounds for the ability to prevent formin-mediated actin assembly in vitro and decreases formin's affinity for the barbed end.

TL;DR: A global analysis of the validated RVxf-based PP1 interactome provided insights into the conserved features of the RVxF motif but also led to the discovery of additional common PP1 binding elements, described as the "SILK" and "MyPhoNE" motifs that contribute to the design of PP1 interaction networks.

TL;DR: Ginkgolic acid and anacardic acid inhibit protein SUMOylation both in vitro and in vivo without affecting in vivo ubiquitination.

TL;DR: It is indicated that MAGL exerts tissue-dependent control over endocannabinoid and monoglyceride metabolism and JZL184 is designated as a selective tool to characterize the functions of MAGL in vivo.

TL;DR: The evolution of far-red fluorescent proteins with peak excitation at 600 nm or above are reported, and the brightest one, Neptune, performs well in imaging deep tissues in living mice and reveals a novel mechanism for red-shifting involving the acquisition of a new hydrogen bond with the acylimine region of the chromophore.

TL;DR: This work describes a cell-based kinetic profiling approach using impedance readout for monitoring the effect of small molecule compounds and indicates that the TCRP approach provides predictive mechanistic information for small molecules compounds.

TL;DR: The data suggest that GSK3 inhibition is the sole activation mode of BR signaling and argues against GSK2-independent BR responses in Arabidopsis, and bikinin represents a useful tool to further unravel regulatory mechanisms.

TL;DR: The unconventional role of DNA as a biologically inspired synthetic enzyme, which can adopt many other types of structures, including some that have been shown to catalyze chemical transformations, is explored.

TL;DR: Fluorescence-based screening demonstrated that Gal-1 recognizes a wide variety of complex N-glycans, whereas Gal-3 primarily recognizes poly-N-acetyllactosamine-containing glycans independent of N- glycan presentation.

TL;DR: The analysis suggests that fatostatin inhibits the ER-Golgi translocation of SREBPs through binding to their escort protein, the SREBP cleavage-activating protein (SCAP), at a distinct site from the sterol-binding domain.

TL;DR: This review summarizes the methodology and recent progress in expanding this technology to eukaryotic cells with reports on labeling and modifying proteins, probing protein structure and function, identifying and regulating protein activity, and generating proteins with new properties.

TL;DR: Structural-activity modeling of the structural features determining the activity of tethered peptides indicated that the extent and positioning of positive charges and hydrophobic residues were influential in determining activity.

TL;DR: The paradigm generality for thiopeptide biosynthesis was supported by genome mining and ultimate confirmation of the thiocillin I production in Bacillus cereus ATCC 14579, a strain that was previously unknown as a thiopedide producer.

TL;DR: The restricted environments channel the reactions of intermediates in Cavitands along a specific path and strengthen the parallels between functional synthetic cavitands and enzymes.

TL;DR: The intracellular hemoglobinolytic cascade in the tick Ixodes ricinus, a vector of Lyme disease and tick-borne encephalitis, is deconvoluted and enzymes identified are potential targets to developing novel anti-tick vaccines.

TL;DR: It is shown that cytotoxicity of proteasome inhibitors does not correlate with inhibition of chymotrypsin-like sites and that coinhibition of either trypsin in-like and/or caspase-like Sites is needed to achieve maximal cytot toxicity, and caspases must be considered as cotargets of anticancer drugs.

TL;DR: Molecular dynamics pointed to the functional relevance of residues located in or close to the beta5-beta6 loop and allowed us to propose a mechanism for carbapenem hydrolysis by OXA-48.

TL;DR: Monitoring the unfolding of protein subunits, using ion mobility-MS, allows differentiation of the effects of ligand binding not normally observed by MS alone, and has implications for small-molecule drug design directed at multiprotein targets.

TL;DR: The fields of RNA biology and nucleic acid engineering, along with the tremendous interdisciplinary growth of synthetic biology, are fueling advances in the emerging field of RNA programming in living systems.

TL;DR: The antigenicity of glycerol monomycolate (GroMM), which stimulates CD1b-restricted CD4(+) T cell clones, is described and it is suggested that GroMM-specific T cells are primed during infection and their detection correlates with lack of clinical active disease.

TL;DR: It is reported here that amitriptyline, an antidepressant drug, directly binds TrkA and TrkB and triggers their dimerization and activation and possesses marked neurotrophic activity.

TL;DR: These findings suggest that the trafficking of anandamide from the plasma membrane to the internal compartments of a cell occur via a nonvesicular mechanism mediated by cytosolic carriers.

TL;DR: Crystal structures of the ligand binding domain of LasR in complex with the autoinducer N-3-oxo-dodecanoyl homoserine lactone provide a molecular rationale for understanding how chemically distinct compounds can be accommodated by a highly selective receptor, and provide the framework for the development of novel quorum-sensing regulators, utilizing the triphenyl scaffold.

TL;DR: In this article, the Sunflower trypsin inhibitor was designed using a combination of molecular modeling and sparse matrix substrate screening to selectively block the proteolytic activity of KLK4 and prevent stimulation of PAR activity in a cell-based system.

TL;DR: Chemical approaches to identify the HDAC enzyme target of HDAC inhibitors show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia and Huntington's disease.

TL;DR: The results demonstrate that mycolic acid methyltransferases are a promising antibiotic target and that a family of virulence factors can be chemically inhibited with effects not anticipated from studies of each individual enzyme.

TL;DR: The global mutagenic approach revealed a low overall specificity of the biosynthetic machinery and important structure-stability correlations in capistruin biosynthesis.

TL;DR: These results provide a vantage point for understanding how much of the diversity of the bisindole class is generated from a small number of diverging pathways from L-tryptophan, as well as enabling identification of bisindoles that are likely derived via completely distinct biosynthetic pathways.

TL;DR: The details of the differential coregulator interactions imposed on the receptor by the ligands are revealed and it is shown that the anchoring of H12 is fundamentally distinct in the presence of the two ligands, thus accounting for the observed effects on coactivator and corepressor interactions.