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  • 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
  • Development of a quantitative approach to determine how far a signal from a cell travels as a diffusible molecule reveals a millimeter-scale quorum sensing mechanism that determines collective growth of differentiating embryonic stem cells.

    • Hirad Daneshpour
    • Pim van den Bersselaar
    • Hyun Youk
    Article Open Access
  • DNA damage results in the acetylation of the cell-cycle checkpoint kinase WEE1 at Lys177 enabling activation. The deacetylase SIRT1 directly associates with and modifies WEE1 to inactivate it enabling resistance to WEE1 inhibition in cancer cells.

    • Xiaomei Zhu
    • Qunshu Su
    • Ting Liu
    Article
  • Tryptophan C-mannosyltransferase (CMT) enzymes append a mannose to the first tryptophan of select sequences, which is important for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. A study reveals the structure, mode of peptide recognition and catalytic mechanism for the eukaryotic C-mannosyltransferase DPY19.

    • Joël S. Bloch
    • Alan John
    • Kaspar P. Locher
    Article Open Access
  • Heparan sulfate proteoglycans are extended disaccharide co-polymers containing decorations of sulfation and epimerization linked to cell surface and extracellular matrix proteins that contribute to cell signaling and tissue homeostasis. This structural and mutagenic study on the EXT1–2 complex explains molecular details of the backbone co-polymer synthesis.

    • Hua Li
    • Digantkumar Chapla
    • Huilin Li
    Article
  • Small-molecule-mediated targeted protein degradation (TPD) relies on the recruitment of a target protein of interest to an E3 ligase. A new study indicates how direct target recruitment to the 26S proteasome can bypass this requirement.

    • Gary Tin
    • Georg E. Winter
    News & Views