Structural response of G protein binding to the cyclodepsipeptide inhibitor FR900359 probed by NMR spectroscopy.

The cyclodepsipeptide FR900359 (FR) and its analogs are able to selectively inhibit the class of G proteins by blocking GDP/GTP exchange. The inhibitor binding site of G has been characterized by X-ray crystallography, and various binding and functional studies have determined binding kinetics and mode of inhibition. Here we investigate isotope-labeled FR bound to the membrane-anchored G protein heterotrimer by solid-state nuclear magnetic resonance (ssNMR) and in solution by liquid-state NMR.

The Bacterial G Signal Transduction Inhibitor FR900359 Impairs Soil-Associated Nematodes.

The cyclic depsipeptide FR900359 (FR) is derived from the soil bacterium Chromobacterium vaccinii and known to bind G proteins of mammals and insects, thereby abolishing the signal transduction of their G protein-coupled receptors, a process that leads to severe physiological consequences. Due to their highly conserved structure, G family of proteins are a superior ecological target for FR producing organisms, resulting in a defense towards a broad range of harmful organisms. Here, we focus on the question whether bacteria like C.

Feature-Based Molecular Networking for the Targeted Identification of G-Inhibiting FR900359 Derivatives.

Both the soil bacterium and the bacterial endosymbiont Burkholderia crenata of the plant are producers of FR900359 (FR). This cyclic depsipeptide is a potent and selective G protein inhibitor used extensively to investigate the intracellular signaling of G protein coupled receptors (GPCRs). In this study, the metabolomes of both FR producers were investigated and compared using feature-based molecular networking (FBMN).

Thioesterase-mediated side chain transesterification generates potent Gq signaling inhibitor FR900359.

The potent and selective Gq protein inhibitor depsipeptide FR900359 (FR), originally discovered as the product of an uncultivable plant endosymbiont, is synthesized by a complex biosynthetic system comprising two nonribosomal peptide synthetase (NRPS) assembly lines. Here we characterize a cultivable bacterial FR producer, enabling detailed investigations into biosynthesis and attachment of the functionally important FR side chain. We reconstitute side chain assembly by the monomodular NRPS FrsA and the non-heme monooxygenase FrsH, and characterize intermolecular side chain transesterification to the final macrocyclic intermediate FR-Core, mediated by the FrsA thioesterase domain.

Outlining where humans live, the World Settlement Footprint 2015.

Human settlements are the cause and consequence of most environmental and societal changes on Earth; however, their location and extent is still under debate. We provide here a new 10 m resolution (0.32 arc sec) global map of human settlements on Earth for the year 2015, namely the World Settlement Footprint 2015 (WSF2015).

Antimicrobial Dialkylresorcins from Marine-Derived Microorganisms: Insights into Their Mode of Action and Putative Ecological Relevance.

has been reported as a seaweed-associated or marine-derived species with largely unknown secondary metabolites. The combination of bioinformatic analysis and MS- and bioactivity guided separation led to the isolation of a new antibiotically active dialkylresorcin from the marine bacterium . The antibiotic profile of the new dialkylresorcin zobelliphol (1: ) was investigated and compared with related and naturally occurring dialkyresorcins (i.

The impact of livestock grazing on plant diversity: an analysis across dryland ecosystems and scales in southern Africa.

A general understanding of grazing effects on plant diversity in drylands is still missing, despite an extensive theoretical background. Cross-biome syntheses are hindered by the fact that the outcomes of disturbance studies are strongly affected by the choice of diversity measures, and the spatial and temporal scales of measurements. The aim of this study is to overcome these weaknesses by applying a wide range of diversity measures to a data set derived from identical sampling in three distinct ecosystems.

[Self-selection processes in the choice of the therapeutic training approach: differences in therapeutic attitudes, personality traits and attributional complexity].

Aim: Treatment approaches differ to a great extent in terms of basic psychological assumptions and practical procedures. This creates questions about the fitting of therapist and therapeutic approach. This paper examines the influence of therapeutic attitudes, mentalization interest and personality traits on the decision for an approach.