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  • Etoposide, a chemotherapeutic poison of type IIA eukaryotic topoisomerases (topo IIs), promotes topo II to compact DNA by trapping DNA loops, creates DNA double-strand breaks, causes topo II to resist relocation, and pauses the ability of topoisomerases to relax DNA supercoiling. Through these mechanisms, etoposide converts topo II into a roadblock to DNA processing.

    Research Briefing
  • Using single-molecule biophysics methods, Le et al. discovered that etoposide, a chemotherapeutic poison of topoisomerase II (topo II), promotes topo II to compact DNA, trap DNA loops and pause DNA supercoiling relaxation, thus converting topo II into a strong roadblock to DNA processing.

    • Tung T. Le
    • Meiling Wu
    • Michelle D. Wang
    Article Open Access
  • A new biosynthetic core-forming enzyme, arginine cyclodipeptide synthase (RCDPS), was found to produce cyclo-arginine-Xaa dipeptides via a tRNA-dependent mechanism, and further genome mining using RCDPS as a beacon uncovered new natural products.

    • Danielle A. Yee
    • Kanji Niwa
    • Yi Tang
    Article
  • The multistep incorporation process of the catalytic NiFe(CN)2(CO) cofactor into [NiFe]-hydrogenase was deciphered by isolating key maturation intermediates, which were characterized by biochemical and a variety of spectroscopic techniques.

    • Giorgio Caserta
    • Sven Hartmann
    • Oliver Lenz
    Article
  • The F420-dependent sulfite reductase protects some methanogenic archaea by converting toxic sulfite. Structural analysis reveals how the two active centers are electro-connected and provides a plausible picture of a primitive sulfite reductase.

    • Marion Jespersen
    • Antonio J. Pierik
    • Tristan Wagner
    Article Open Access
  • GPCRs are selective for specific G-protein subtypes, thereby ensuring signaling fidelity. A new report finds that that empty-like G-protein mutants are promiscuously recognized by GPCRs, suggesting that receptors select cognate over non-cognate G proteins at steps preceding nucleotide release.

    • Mikel Garcia-Marcos
    News & Views
  • Modern drug discovery relies upon intelligent exploration of ‘in stock’ and ‘on demand’ virtual libraries of compounds. A comparative analysis highlights the explosive expansion of accessible chemical space and also reveals challenges and opportunities arising for computational drug discovery.

    • Artem Cherkasov
    News & Views
  • A near-atomic resolution strain-specific cryo-EM structure of infectious prion fibrils from mice was determined, revealing a structural definition for intra-species prion strain-specific conformations.

    • Szymon W. Manka
    • Adam Wenborn
    • Jonathan D. F. Wadsworth
    Article Open Access
  • Docking virtual libraries against protein structures has identified potent ligands for multiple targets. A comprehensive analysis reveals that the increased size of virtual libraries improves receptor fit but diverges from bio-like molecules.

    • Jiankun Lyu
    • John J. Irwin
    • Brian K. Shoichet
    Article
  • Analysis of cell–cell communication between embryonic stem cells using a combination of experiments and modeling shows that cells can communicate important messages over much larger distances than previously known, exhibiting quorum-sensing-like behavior.

    • Adam L. MacLean
    News & Views