Small molecule antagonists in distinct binding modes inhibit drug-resistant mutant of smoothened

1. Download : Download high-res image (107KB)
2. Download : Download full-size image

Highlights? New small molecule antagonists of Smo with distinct binding modes discovered from high throughput screens ? ALLO-1 and ALLO-2 are potent against the drug-resistant mutant of Smo ? ALLO-1 is potent against oncogenic mutant of Smo (SmoM2)     

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

1. Download : Download high-res image (116KB)
2. Download : Download full-size image

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

1. Download : Download high-res image (166KB)
2. Download : Download full-size image

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     

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

1. Download : Download high-res image (135KB)
2. Download : Download full-size image

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     

A LOV2 Domain-Based Optogenetic Tool to Control Protein Degradation and Cellular Function

1. Download : Download high-res image (288KB)
2. Download : Download full-size image

Highlights? Optogenetic tool to control the stability of soluble and membrane proteins ? Engineered using the LOV2 domain and a murine ornithine decarboxylase-like degron ? Creation of light-switchable, conditional mutants ? Graded response to very low blue light intensities allows yeast photography     

Development of Antibiotic Activity Profile Screening for the Classification and Discovery of Natural Product Antibiotics

1. Download : Download high-res image (165KB)
2. Download : Download full-size image

Highlights? Antibiotics can be classified by structural class based on biological fingerprints ? BioMAP predicts the presence of known compounds in natural product extracts ? BioMAP reveals compounds with unique antibacterial properties ? A naphthoquinone antibiotic with a unique carbon skeleton has been discovered     

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

1. Download : Download high-res image (283KB)
2. Download : Download full-size image

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     

A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

1. Download : Download high-res image (173KB)
2. Download : Download full-size image

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     

Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution

1. Download : Download high-res image (187KB)
2. Download : Download full-size image

Highlights? Microfluidic droplet compartments miniaturize cell lysate screening assays ? Picoliter single-cell lysate assays comparable in sensitivity to macroscale ? Directed evolution results in improved clones validating this experimental set-up ? Precision of droplet sorting enables enrichment of clones with slight improvements     

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

1. Download : Download high-res image (181KB)
2. Download : Download full-size image

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

1. Download : Download high-res image (278KB)
2. Download : Download full-size image

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     

Terpendole E,a Kinesin Eg5 Inhibitor,Is a Key Biosynthetic Intermediate of Indole-Diterpenes in the Producing Fungus Chaunopycnis alba

1. Download : Download high-res image (212KB)
2. Download : Download full-size image

Highlights? The terpendole biosynthetic gene cluster was isolated ? Terpendole E is a key biosynthetic intermediate of indole-diterpenes ? Terpendole E was overproduced by gene knockout of the bispecific enzyme TerP ? Indole-diterpene biosynthetic pathways can be classified into two groups     

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

1. Download : Download high-res image (224KB)
2. Download : Download full-size image

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     

Structural Properties of Model Phosphatidylcholine Flippases

1. Download : Download high-res image (365KB)
2. Download : Download full-size image

Highlights? Model peptides induce sequence-dependent flip of lipids with different headgroups ? Flip activity of peptides depends on the lipid composition of the host membrane ? SNARE proteins have lipid flippase activity     

CXCR4 Stimulates Macropinocytosis: Implications for Cellular Uptake of Arginine-Rich Cell-Penetrating Peptides and HIV

1. Download : Download high-res image (261KB)
2. Download : Download full-size image

Highlights? CXCR4 was identified as a receptor to stimulate cellular uptake of R12 peptide ? Interaction with R12 stimulates internalization of CXCR4 via macropinocytosis ? SDF-1α and HIV-1 gp120 protein also induce macropinocytosis ? Macropinocytic uptake of HIV-1 diminished the infection of host cells     

Discovery of Peptoid Ligands for Anti-Aquaporin 4 Antibodies

1. Download : Download high-res image (81KB)
2. Download : Download full-size image

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     

Cysteine Reactivity Distinguishes Redox Sensing by the Heat-Inducible and Constitutive Forms of Heat Shock Protein 70

1. Download : Download high-res image (205KB)
2. Download : Download full-size image

Highlights? The stress-inducible chaperone Hsp72, but not constitutive Hsc70, is prone to oxidation ? Specific cysteine residues in Hsp72 may be important in redox sensing ? Oxidation of Hsp72 causes degradation of its substrate, tau, in cells     

BTZO-1, a cardioprotective agent, reveals that macrophage migration inhibitory factor regulates ARE-mediated gene expression

1. Download : Download high-res image (190KB)
2. Download : Download full-size image

Highlights? ARE activation is involved in cellular protection against oxidative stress ? MIF is a ubiquitous protein with conserved nucleophilic Pro1 in a hydrophobic pocket ? BTZO-1 selectively binds to MIF, and its binding required the intact N-terminal Pro1 ? Binding of BTZO-1 to MIF leads to the ARE activation in cardiomyocytes.     

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

1. Download : Download high-res image (359KB)
2. Download : Download full-size image

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     

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

1. Download : Download high-res image (154KB)
2. Download : Download full-size image

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