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    1. Biochemistry and Chemical Biology

    Action of CMG with strand-specific DNA blocks supports an internal unwinding mode for the eukaryotic replicative helicase

    Lance Langston, Mike O’Donnell
    The CMG complex, the replicative helicase in eukaryotes, uses a different mechanism from bacterial and viral helicases by engaging both strands of parental DNA with substantial force and unwinding the duplex within the central channel of CMG.
    1. Biochemistry and Chemical Biology

    In vitro reconstitution reveals major differences between human and bacterial cytochrome c synthases

    Molly C Sutherland, Deanna L Mendez ... Robert G Kranz
    Despite the known heme attachment motif (CXXCH) in all c-type cytochromes, attachment elements recognized by human and bacterial cytochrome c biogenesis pathways are distinct, providing clear targets for differential inhibitors.
    1. Biochemistry and Chemical Biology

    Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

    Qiang Liu, Jin Wang ... Jing Yao
    Identifying and understanding that local anesthetic dyclonine targets TRPV3 channels will help to conceive therapeutic interventions.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Activity-based CRISPR scanning uncovers allostery in DNA methylation maintenance machinery

    Kevin Chun-Ho Ngan, Samuel M Hoenig ... Brian B Liau
    Activity-based inhibitors, in conjunction with new experimental and computational tools, enable the discovery of mechanisms involved in DNMT1 autoinhibition.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural basis of GSK-3 inhibition by N-terminal phosphorylation and by the Wnt receptor LRP6

    Jennifer L Stamos, Matthew Ling-Hon Chu ... William I Weis
    Phosphorylation of the Wnt receptor LRP6 directly inhibits glycogen synthase kinase-3 by acting as a pseudosubstrate that stabilizes an active conformation of the enzyme, identical to autoinhibition by phosphorylation of its N terminus.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    GE23077 binds to the RNA polymerase ‘i’ and ‘i+1’ sites and prevents the binding of initiating nucleotides

    Yu Zhang, David Degen ... Richard H Ebright
    The cyclic-peptide antibiotic GE23077 inhibits bacterial RNA polymerase through a novel target that exhibits low susceptibility to target-based resistance and that enables synthesis of bipartite inhibitors that are exceptionally potent and refractory to target-based resistance.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain

    Boris Brumshtein, Shannon R Esswein ... David S Eisenberg
    Ligands that bind dimers of light chain variable domains inhibit the formation of amyloid fibrils.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch

    Sandeep K Talapatra, Bethany Harker, Julie PI Welburn
    Structural analysis of the kinesin-13 MCAK bound to its C-terminal tail reveals the molecular basis for the conformation of kinesin-13 in solution and the mechanism that triggers long-range conformational changes upon microtubule binding.
    1. Cell Biology
    2. Neuroscience

    Small molecule induced oligomerization, clustering and clathrin-independent endocytosis of the dopamine transporter

    Tatiana Sorkina, Shiqi Ma ... Alexander Sorkin
    Dopamine transporter (DAT) interaction with furopyrimidine called AIM-100 in intact cells leads to dramatic oligomerization, nanoclustering and endocytosis of DAT by a novel mechanism coupled to the transporter molecule conformation.
    1. Cell Biology

    Progesterone induces meiosis through two obligate co-receptors with PLA2 activity

    Nancy Nader, Lama Assaf ... Khaled Machaca
    Progesterone mediates nongenomic signaling in Xenopus oocyte meiosis by activating a PLA2 activity that requires two membrane receptors ABDH2 and mPRß.