Now showing items 1-20 of 39

    • A >200 meV Uphill Thermodynamic Landscape for Radical Transport in Escherichia coli Ribonucleotide Reductase Determined Using Fluorotyrosine-Substituted Enzymes 

      Ravichandran, Kanchana R.; Taguchi, Alexander T.; Wei, Yifeng; Tommos, Cecilia; Nocera, Daniel G.; Stubbe, JoAnne (American Chemical Society, 2016)
      Escherichia coli class Ia ribonucleotide reductase (RNR) converts ribonucleotides to deoxynucleotides. A diferric-tyrosyl radical (Y122•) in one subunit (β2) generates a transient thiyl radical in another subunit (α2) via ...
    • Antimicrobial Chemicals Are Associated with Elevated Antibiotic Resistance Genes in the Indoor Dust Microbiome 

      Hartmann, Erica M.; Hickey, Roxana; Hsu, Tiffany; Betancourt Román, Clarisse M.; Chen, Jing; Schwager, Randall; Kline, Jeff; Brown, G. Z.; Halden, Rolf U.; Huttenhower, Curtis; Green, Jessica L. (American Chemical Society, 2016)
      Antibiotic resistance is increasingly widespread, largely due to human influence. Here, we explore the relationship between antibiotic resistance genes and the antimicrobial chemicals triclosan, triclocarban, and methyl-, ...
    • Controlled Growth of Filamentous Fatty Acid Vesicles under Flow 

      Hentrich, Christian; Szostak, Jack W. (American Chemical Society, 2014)
      The earliest forms of cellular life would have required a membrane compartment capable of growth and division. Fatty acid vesicles are an attractive model of protocell membranes, as they can grow into filamentous vesicles ...
    • Developmental regulation of myeloerythroid progenitor function by the Lin28b–let-7–Hmga2 axis 

      Rowe, R. Grant; Wang, Leo D.; Coma, Silvia; Han, Areum; Mathieu, Ronald; Pearson, Daniel S.; Ross, Samantha; Sousa, Patricia; Nguyen, Phi T.; Rodriguez, Antony; Wagers, Amy J.; Daley, George Q. (The Rockefeller University Press, 2016)
      For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in ...
    • Discovery of a Small-Molecule Probe for V-ATPase Function 

      Aldrich, Leslie N.; Kuo, Szu-Yu; Castoreno, Adam B.; Goel, Gautam; Kuballa, Petric; Rees, Matthew G.; Seashore-Ludlow, Brinton A.; Cheah, Jaime H.; Latorre, Isabel J.; Schreiber, Stuart L.; Shamji, Alykhan F.; Xavier, Ramnik J. (American Chemical Society, 2015)
      Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been ...
    • Discovery of Human sORF-Encoded Polypeptides (SEPs) in Cell Lines and Tissue 

      Ma, Jiao; Ward, Carl C.; Jungreis, Irwin; Slavoff, Sarah A.; Schwaid, Adam G.; Neveu, John; Budnik, Bogdan A.; Kellis, Manolis; Saghatelian, Alan (American Chemical Society, 2014)
      The existence of nonannotated protein-coding human short open reading frames (sORFs) has been revealed through the direct detection of their sORF-encoded polypeptide (SEP) products. The discovery of novel SEPs increases ...
    • Discovery of Small-Molecule Modulators of the Sonic Hedgehog Pathway 

      Schaefer, Giannina I.; Perez, José R.; Duvall, Jeremy R.; Stanton, Benjamin Z.; Shamji, Alykhan F.; Schreiber, Stuart L. (American Chemical Society, 2013)
      The Hedgehog signaling pathway is involved in the development of multicellular organisms and, when deregulated, can contribute to certain cancers, among other diseases. The molecular characterization of the pathway, which ...
    • Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2) 

      Tan, Li; Nomanbhoy, Tyzoon; Gurbani, Deepak; Patricelli, Matthew; Hunter, John; Geng, Jiefei; Herhaus, Lina; Zhang, Jianming; Pauls, Eduardo; Ham, Youngjin; Choi, Hwan Geun; Xie, Ting; Deng, Xianming; Buhrlage, Sara J.; Sim, Taebo; Cohen, Philip; Sapkota, Gopal; Westover, Kenneth D.; Gray, Nathanael S. (American Chemical Society, 2014)
      We developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a ...
    • Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents 

      Comer, Eamon; Beaudoin, Jennifer A.; Kato, Nobutaka; Fitzgerald, Mark E.; Heidebrecht, Richard W.; Lee, Maurice duPont; Masi, Daniela; Mercier, Marion; Mulrooney, Carol; Muncipinto, Giovanni; Rowley, Ann; Crespo-Llado, Keila; Serrano, Adelfa E.; Lukens, Amanda K.; Wiegand, Roger C.; Wirth, Dyann F.; Palmer, Michelle A.; Foley, Michael A.; Munoz, Benito; Scherer, Christina A.; Duvall, Jeremy R.; Schreiber, Stuart L. (American Chemical Society, 2014)
      Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic ...
    • First Passage Analysis of the Folding of a β-Sheet Miniprotein: Is it More Realistic Than the Standard Equilibrium Approach? 

      Kalgin, Igor V.; Chekmarev, Sergei F.; Karplus, Martin (American Chemical Society, 2014)
      Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are ...
    • Flash Memory: Photochemical Imprinting of Neuronal Action Potentials onto a Microbial Rhodopsin 

      Venkatachalam, Veena; Brinks, Daan; Maclaurin, Dougal; Hochbaum, Daniel; Kralj, Joel; Cohen, Adam E. (American Chemical Society, 2014)
      We developed a technique, “flash memory”, to record a photochemical imprint of the activity state—firing or not firing—of a neuron at a user-selected moment in time. The key element is an engineered microbial rhodopsin ...
    • High-Throughput Screen in Cryptococcus neoformans Identifies a Novel Molecular Scaffold That Inhibits Cell Wall Integrity Pathway Signaling 

      Hartland, Kate; Pu, Jun; Palmer, Michelle; Dandapani, Sivaraman; Moquist, Philip N.; Munoz, Benito; DiDone, Louis; Schreiber, Stuart L.; Krysan, Damian J. (American Chemical Society, 2015)
      Cryptococcus neoformans is one of the most important human fungal pathogens; however, no new therapies have been developed in over 50 years. Fungicidal activity is crucially important for an effective anticryptococal agent ...
    • The histone demethylase LSD1/KDM1A promotes the DNA damage response 

      Mosammaparast, Nima; Kim, Haeyoung; Laurent, Benoit; Zhao, Yu; Lim, Hui Jun; Majid, Mona C.; Dango, Sebastian; Luo, Yuying; Hempel, Kristina; Sowa, Mathew E.; Gygi, Steven P.; Steen, Hanno; Harper, J. Wade; Yankner, Bruce; Shi, Yang (The Rockefeller University Press, 2013)
      Histone demethylation is known to regulate transcription, but its role in other processes is largely unknown. We report a role for the histone demethylase LSD1/KDM1A in the DNA damage response (DDR). We show that LSD1 is ...
    • Identification of Ligand–Target Pairs from Combined Libraries of Small Molecules and Unpurified Protein Targets in Cell Lysates 

      McGregor, Lynn M.; Jain, Tara; Liu, David R. (American Chemical Society, 2014)
      We describe the development and validation of interaction determination using unpurified proteins (IDUP), a method that selectively amplifies DNA sequences identifying ligand+target pairs from a mixture of DNA-linked small ...
    • In Vivo Metabolic Fingerprinting of Neutral Lipids with Hyperspectral Stimulated Raman Scattering Microscopy 

      Fu, Dan; Yu, Yong; Folick, Andrew; Currie, Erin; Farese, Robert V.; Tsai, Tsung-Huang; Xie, Xiaoliang Sunney; Wang, Meng C. (American Chemical Society, 2014)
      Metabolic fingerprinting provides valuable information on the physiopathological states of cells and tissues. Traditional imaging mass spectrometry and magnetic resonance imaging are unable to probe the spatial-temporal ...
    • Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade 

      Guo, Peng; You, Jin-Oh; Yang, Jiang; Jia, Di; Moses, Marsha A.; Auguste, Debra T. (American Chemical Society, 2014)
      Because breast cancer patient survival inversely correlates with metastasis, we engineered vehicles to inhibit both the C-X-C chemokine receptor type 4 (CXCR4) and lipocalin-2 (Lcn2) mediated migratory pathways. pH-responsive ...
    • Kinetics of Hydrogen Atom Abstraction from Substrate by an Active Site Thiyl Radical in Ribonucleotide Reductase 

      Olshansky, Lisa; Pizano, Arturo A.; Wei, Yifeng; Stubbe, JoAnne; Nocera, Daniel G. (American Chemical Society, 2014)
      Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms. Active E. coli class Ia RNR is an α2β2 complex that undergoes reversible, long-range proton-coupled electron ...
    • Kinetics of Hydrogen Atom Abstraction from Substrate by an Active Site Thiyl Radical in Ribonucleotide Reductase 

      Olshansky, Lisa; Pizano, Arturo A.; Wei, Yifeng; Stubbe, JoAnne; Nocera, Daniel G. (American Chemical Society, 2014)
      Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides in all organisms. Active E. coli class Ia RNR is an α2β2 complex that undergoes reversible, long-range proton-coupled electron ...
    • Late Oligocene and Early Miocene Muroidea of the Zinda Pir Dome 

      Lindsay, Everett H.; Flynn, Lawrence J. (Taylor & Francis, 2015)
      A series of Oligocene through Early Miocene terrestrial deposits preserved in the foothills of the Zinda Pir Dome of western Pakistan produce multiple, superposed fossil mammal localities. These include small mammal ...
    • Mechanism of Germacradien-4-ol Synthase-Controlled Water Capture 

      Grundy, Daniel J.; Chen, Mengbin; González, Verónica; Leoni, Stefano; Miller, David J.; Christianson, David W.; Allemann, Rudolf K. (American Chemical Society, 2016)
      The sesquiterpene synthase germacradiene-4-ol synthase (GdolS) from Streptomyces citricolor is one of only a few known high-fidelity terpene synthases that convert farnesyl diphosphate (FDP) into a single hydroxylated ...