ALDH2 Mediates 5-Nitrofuran Activity in Multiple Species

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Highlights? Zebrafish provide a viable assay for the biological toxicity of 5-nitrofurans ? ALDH2 inhibitors prevent 5-nitrofuran toxicity in zebrafish and yeast ? Genetic dependence on ALDH2 for 5-nitrofuran toxicity in zebrafish and yeast systems ? 5-Nitrofurans bind to and are substrates of human ALDH2     

A Synthetic Substrate of DNA Polymerase Deviating from the Bases,Sugar, and Leaving Group of Canonical Deoxynucleoside Triphosphates

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Highlights? A highly modified nucleotide as substrate for polymerases ? The reversibility of the polymerase reaction at the template level ? Synthesis of a nucleoside with two anomeric centers     

Identification of exosite-targeting inhibitors of anthrax lethal factor by high-throughput screening

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Highlights? Development of an assay for LF protease using a full-length protein substrate ? Lichen depsidones identified as exosite-targeting LF inhibitors ? Exosite inhibitors protect macrophages from LF cytotoxicity     

Reconstitution of Nucleosome Demethylation and Catalytic Properties of a Jumonji Histone Demethylase

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Highlights? Catalytic domain of JMJD2A (cJMJD2A) removes methyl marks in a distributive manner ? Homogeneously methylated nucleosomes were used as substrates ? Quantitative assay for nucleosome demethylation has been developed     

Fluorescence Imaging of Single-Copy DNA Sequences within the Human Genome Using PNA-Directed Padlock Probe Assembly

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Highlights? PNA-directed assembly of the labeling complex on duplex DNA ? Padlock probes combined with rolling circle amplification for signal amplification ? Multitarget visualization within the human genome with high sequence selectivity     

Insights into a Divergent Phenazine Biosynthetic Pathway Governed by a Plasmid-Born Esmeraldin Gene Cluster

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Highlights? Esm gene cluster resides on a highly unstable giant plasmid ? EsmA1 and A2 work together to promote the formation of phenazine-1,6-dicarboxylic acid ? Polyketide synthase enzymes EsmB1–B5 catalyze the unique methyl transfer ? Atypical polyketide synthase enzymes EsmD1–D3 catalyze the esterification.     

Discovery of Peptoid Ligands for Anti-Aquaporin 4 Antibodies

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Highlights? Peptoid ligands for anti-AQP4 autoantibodies that drive NMO have been identified ? Some of these peptoids provide an accurate blood test for the disease     

Chemical Proteomics with Sulfonyl Fluoride Probes Reveals Selective Labeling of Functional Tyrosines in Glutathione Transferases

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Highlights? Sulfonyl fluoride probes label diverse GSTs in both plant and mouse proteomes ? GSTs are labeled on Tyr residues in unconserved substrate binding pockets ? Labeled Tyr residues are essential for GST function     

A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

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Highlights? Growth arrest induced by human telomerase in yeast is chemically reversible ? Readout is sensitive to telomerase catalytic activity and telomere recruitment ? Three cell-permeable compounds also inhibit purified human telomerase ? Yeast can be successfully used to screen for human telomerase inhibitors     

Structures of Cyanobactin Maturation Enzymes Define a Family of Transamidating Proteases

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Highlights? Boundaries for cyanobactin maturation protease domains determined ? Structures of protease domains for cyanobactin maturation enzymes determined ? Additional structural motif in PatG assists in cyclizing transamidation ? Rational mutagenesis of active site leads to altered catalytic profiles for PatG     

Targeted Single-Cell Microchemical Analysis: MS-Based Peptidomics of Individual Paraformaldehyde-Fixed and Immunolabeled Neurons

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Highlights? Investigation of archived biological tissue at the single-cell level ? Screening of neuropeptides from immunolabeled tissue preserved up to 42 weeks ? Validation of antibody specificity using mass spectrometric approaches ? Standardized protocols for comprehensive characterization of selected cells     

Prohibitin Ligands in Cell Death and Survival: Mode of Action and Therapeutic Potential

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Highlights? Prohibitins regulate cell survival, metabolism, and inflammation ? Prohibitins act as a hub for many signaling pathways ? Prohibitin ligands are examined in cancer, Parkinson’s disease, and obesity     

Morphobase,an Encyclopedic Cell Morphology Database,and Its Use for Drug Target Identification

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Highlights? Development of an encyclopedia of cell morphology, Morphobase ? Small molecules classified by mode of action with Morphobase ? Morphobase system rapidly predicts molecular targets of compounds ? NPD6689 targets tubulin and is a lead for a class of antitubulin drugs     

Interplay between the Ribosomal Tunnel,Nascent Chain,and Macrolides Influences Drug Inhibition

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Highlights? Macrolides exhibit nascent polypeptide chain–dependent inhibition ? Peptides can form specific interactions with the ribosomal tunnel ? A covalent bond between tylosin and the ribosome is necessary for inhibitory activity     

Structural and functional investigation of the intermolecular interaction between NRPS adenylation and carrier protein domains

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Highlights? Crystallographic structure of NRPS adenylation and PCP domain interface ? NRPS adenylation C-terminal domain rotation creates appropriate PCP interface ? Mechanism-based inhibitor traps conformationally flexible proteins ? Structure-guided mutagenesis improves noncognate NRPS interactions     

Unveiling the post-PKS redox tailoring steps in biosynthesis of the type II polyketide antitumor antibiotic xantholipin

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Highlights? Cloning and sequencing of the complete xantholipin biosynthesis gene cluster ? Identification of genes for xanthone and methylenedioxy bridge formation ? An unusual C11 ketoreductase for the prearomatic reduction ? Multiple redox tailoring for type II PKS biosynthesis     

Recycling of Informational Units Leads to Selection of Replicators in a Prebiotic Soup

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Highlights? Recycling of genetic material is important for the origins of life ? Simulation studies show recycling leads to the selection of genotypes from a pool ? Recycling can lead to the sudden emergence of a high-fitness RNA genotype ? Experimental studies with the Azoarcus ribozyme show fragment recycling     

Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2

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Highlights? CPYPP binds to DOCK2 DHR-2 domain and inhibits its catalytic activity ? CPYPP inhibits DOCK2-mediated Rac activation in cells ? The structural features of CPYPP required for its inhibitory effect were revealed ? CPYPP inhibits lymphocyte migration and activation in vitro and in vivo     

A Substrate-Inspired Probe Monitors Translocation,Activation, and Subcellular Targeting of Bacterial Type III Effector Protease AvrPphB

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Highlights? Bacterial papain-like protease AvrPphB cleaves kinases in host plant cell ? Activity-based probe for AvrPphB inspired on its unique substrate specificity ? Secretion of ProAvrPphB through narrow type III pilus requires prodomain ? Prodomain removal is essential to trigger cell death in resistant plants     

Biomembrane interactions reveal the mechanism of action of surface-immobilized host defense IDR-1010 peptide

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Highlights? Biomembrane interactions of surface-tethered host defense peptides are studied ? Polymer brush-tethered IDR-1010cys showed enhanced biomembrane interactions ? Mechanism of action of surface-tethered peptides is different from its soluble form