July 31, 2007 ͉ vol. 104 ͉ no. 31 ͉ 12583–12950 Proceedings of the National Academy ofPNAS Sciences of the United States of America www.pnas.org Cover image: Single-molecule observation of catalytic turnover. The wide-field image was recorded during hydrolysis of fluorescein esters on a catalytic monolayer. Individual turnover events appear as isolated bright spots. Microscopic and spectroscopic studies of enzymes and inorganic agents provide evidence that catalysts, even of uniform composition, are ensembles possessing a range of activities. See the Perspective by Roeffaers et al. on pages 12603–12609. Image courtesy of Hiroshi Uji-i. From the Cover 12603 Fluorescence spectroscopy of catalysts 12709 DNA mismatch repair 12843 TNF-␣ suppresses clock genes 12942 Human impact on the biosphere SINGLE-MOLECULE CHEMISTRY AND BIOLOGY Contents SPECIAL FEATURE INTRODUCTORY PERSPECTIVE THIS WEEK IN PNAS 12595 Introduction to the Special Feature on Single-Molecule Chemistry and Biology 12583 In This Issue Robert J. Silbey PERSPECTIVES COMMENTARY 12596 New directions in single-molecule imaging and analysis W. E. Moerner 12585 Our share of the planetary pie Jonathan A. Foley, Chad Monfreda, Navin Ramankutty, 12603 Single-molecule fluorescence spectroscopy in (bio)catalysis and David Zaks Maarten B. J. Roeffaers, Gert De Cremer, Hiroshi Uji-i, ➜ See companion article on page 12942 Benıˆot Muls, Bert F. Sels, Pierre A. Jacobs, Frans C. De Schryver, Dirk E. De Vos, and Johan Hofkens RESEARCH ARTICLES INAUGURAL ARTICLE 12610 Single-molecule and ensemble fluorescence assays for a functionally important conformational change 12587 The role of skeletal muscle insulin resistance in the in T7 DNA polymerase pathogenesis of the metabolic syndrome Guobin Luo, Mina Wang, William H. Konigsberg, Kitt Falk Petersen, Sylvie Dufour, David B. Savage, and X. Sunney Xie Stefan Bilz, Gina Solomon, Shin Yonemitsu, Gary W. 12616 Strongly emissive individual DNA-encapsulated Ag Cline, Douglas Befroy, Laura Zemany, Barbara B. nanoclusters as single-molecule fluorophores Kahn, Xenophon Papademetris, Douglas L. Tom Vosch, Yasuko Antoku, Jung-Cheng Hsiang, Rothman, and Gerald I. Shulman Chris I. Richards, Jose I. Gonzalez, and Robert M. Dickson 12622 Principal-components analysis of shape fluctuations of single DNA molecules Freely available online through the PNAS open access option. Adam E. Cohen and W. E. Moerner PNAS ͉ July 31, 2007 ͉ vol. 104 ͉ no. 31 ͉ iii–x Downloaded by guest on September 30, 2021 12628 Local viscosity of supercooled glycerol near Tg probed STATISTICS by rotational diffusion of ensembles and single 12663 Intracellular crowding defines the mode and sequence dye molecules of substrate uptake by Escherichia coli and constrains Rob Zondervan, Florian Kulzer, Gregorius C. G. Berkhout, its metabolic activity and Michel Orrit Q. K. Beg, A. Vazquez, J. Ernst, M. A. de Menezes, Z. Bar-Joseph, A.-L. Baraba´si, and Z. N. Oltvai 12634 Dissecting the multistep reaction pathway of an RNA enzyme by single-molecule kinetic ‘‘fingerprinting’’ Shixin Liu, Gregory Bokinsky, Nils G. Walter, SOCIAL SCIENCES and Xiaowei Zhuang 12640 Single-molecule FRET reveals sugar-induced PSYCHOLOGY conformational dynamics in LacY 12669 Visuomotor system uses target features unavailable Devdoot S. Majumdar, Irina Smirnova, Vladimir to conscious awareness Kasho, Eyal Nir, Xiangxu Kong, Shimon Weiss, Gordon Binsted, Kyle Brownell, Zofia Vorontsova, and H. Ronald Kaback Matthew Heath, and Deborah Saucier 12646 Fueling protein–DNA interactions inside BIOLOGICAL SCIENCES porous nanocontainers Ibrahim Cisse, Burak Okumus, Chirlmin Joo, and Taekjip Ha BIOCHEMISTRY 12651 Probing nucleation, reverse annealing, and chaperone 12610 Single-molecule and ensemble fluorescence assays function along the reaction path of HIV-1 for a functionally important conformational change single-strand transfer in T7 DNA polymerase Yining Zeng, Hsiao-Wei Liu, Christy F. Landes, Guobin Luo, Mina Wang, William H. Konigsberg, Yoen Joo Kim, Xiaojing Ma, Yongjin Zhu, and X. Sunney Xie Karin Musier-Forsyth, and Paul F. Barbara 12673 Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1␣,25-(OH)2D3-26,23-lactone PHYSICAL SCIENCES David E. Prosser, Martin Kaufmann, Brendan O’Leary, Valarie Byford, and Glenville Jones APPLIED MATHEMATICS 12679 Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial 12657 Efficient Monte Carlo sampling by androgen receptor parallel marginalization Chun-Te Wu, Saleh Altuwaijri, William A. Ricke, Jonathan Weare Shu-Pin Huang, Shuyuan Yeh, Caixia Zhang, Yuanjie Niu, Meng-Ying Tsai, 12726 Combinatorial promoter design for engineering noisy and Chawnshang Chang gene expression Kevin F. Murphy, Ga´bor Bala´zsi, and James J. Collins 12685 Crystal structure of the GINS complex and functional insights into its role in DNA replication Y. Paul Chang, Ganggang Wang, Vladimir Bermudez, CHEMISTRY Jerard Hurwitz, and Xiaojiang S. Chen 12610 Single-molecule and ensemble fluorescence assays for a functionally important conformational change 12691 Epigenetic regulation of the Drosophila chromosome 4 in T7 DNA polymerase by the histone H3K9 methyltransferase dSETDB1 Guobin Luo, Mina Wang, William H. Konigsberg, Tsai-Yu Tzeng, Chi-Hua Lee, Li-Wei Chan, and X. Sunney Xie and C.-K. James Shen 12616 Strongly emissive individual DNA-encapsulated Ag 12697 Design of protein–membrane interaction inhibitors by nanoclusters as single-molecule fluorophores virtual ligand screening, proof of concept with the C2 Tom Vosch, Yasuko Antoku, Jung-Cheng Hsiang, domain of factor V Chris I. Richards, Jose I. Gonzalez, Kenneth Segers, Olivier Sperandio, Markus Sack, and Robert M. Dickson Rainer Fischer, Maria A. Miteva, Jan Rosing, Gerry A. F. Nicolaes, and Bruno O. Villoutreix PHYSICS 12703 Phage escape libraries for checkmate analysis Tobin J. Dickerson, Kathleen M. McKenzie, Amanda S. 12622 Principal-components analysis of shape fluctuations Hoyt, Malcolm R. Wood, Kim D. Janda, Sydney B. of single DNA molecules Brenner, and Richard A. Lerner Adam E. Cohen and W. E. Moerner 12709 Protein roadblocks and helix discontinuities are barriers 12628 Local viscosity of supercooled glycerol near Tg probed to the initiation of mismatch repair by rotational diffusion of ensembles and single Anna Pluciennik and Paul Modrich dye molecules Rob Zondervan, Florian Kulzer, Gregorius C. G. Berkhout, 12714 A closer look at energy transduction in muscle and Michel Orrit Hirofumi Onishi and Manuel F. Morales PNAS ͉ July 31, 2007 ͉ vol. 104 ͉ no. 31 ͉ v Downloaded by guest on September 30, 2021 12720 Reevaluating the relationship between EPR spectra 12767 15N photochemically induced dynamic nuclear and enzyme structure for the iron–sulfur clusters polarization magic-angle spinning NMR analysis in NADH:quinone oxidoreductase of the electron donor of photosystem II Gregory Yakovlev, Torsten Reda, and Judy Hirst Anna Diller, Esha Roy, Peter Gast, Hans J. van Gorkom, Huub J. M. de Groot, Clemens Glaubitz, Gunnar BIOPHYSICS Jeschke, Jo¨rg Matysik, and A. Alia 12622 Principal-components analysis of shape fluctuations of single DNA molecules 12772 Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against Adam E. Cohen and W. E. Moerner enfuvirtide-resistant virus 12634 Dissecting the multistep reaction pathway of an RNA John J. Dwyer, Karen L. Wilson, Donna K. Davison, enzyme by single-molecule kinetic ‘‘fingerprinting’’ Stephanie A. Freel, Jennifer E. Seedorff, Stephen A. Shixin Liu, Gregory Bokinsky, Nils G. Walter, Wring, Nicolai A. Tvermoes, Thomas J. Matthews, and Xiaowei Zhuang Michael L. Greenberg, and Mary K. Delmedico 12640 Single-molecule FRET reveals sugar-induced conformational dynamics in LacY CELL BIOLOGY Devdoot S. Majumdar, Irina Smirnova, Vladimir Kasho, Eyal Nir, Xiangxu Kong, Shimon Weiss, 12778 RPA and ATR link transcriptional stress to p53 and H. Ronald Kaback Frederick A. Derheimer, Heather M. O’Hagan, Heather M. Krueger, Sheela Hanasoge, Michelle T. 12646 Fueling protein–DNA interactions inside Paulsen, and Mats Ljungman porous nanocontainers Ibrahim Cisse, Burak Okumus, Chirlmin Joo, and Taekjip Ha 12784 Protein 4.1B suppresses prostate cancer progression and metastasis 12651 Probing nucleation, reverse annealing, and chaperone Sunny Y. Wong, Herbert Haack, Joseph L. Kissil, Marc Barry, function along the reaction path of HIV-1 Roderick T. Bronson, Steven S. Shen, Charles A. Whittaker, single-strand transfer Denise Crowley, and Richard O. Hynes Yining Zeng, Hsiao-Wei Liu, Christy F. Landes, Yoen Joo Kim, Xiaojing Ma, Yongjin Zhu, Karin 12790 Elevated NF-␬B responses and FLIP levels in leukemic but Musier-Forsyth, and Paul F. Barbara not normal lymphocytes: Reduction by salicylate allows 12663 Intracellular crowding defines the mode and sequence TNF-induced apoptosis of substrate uptake by Escherichia coli and constrains Colin Rae, Susana Langa, Steven J. Tucker, its metabolic activity and David J. MacEwan Q. K. Beg, A. Vazquez, J. Ernst, M. A. de Menezes, Z. Bar-Joseph, A.-L. Baraba´si, and Z. N. Oltvai DEVELOPMENTAL BIOLOGY 12726 Combinatorial promoter design for engineering noisy gene expression 12796 Metabolic plasticity during mammalian development Kevin F. Murphy, Ga´bor Bala´zsi, and James J. Collins is directionally dependent on early nutritional status Peter D. Gluckman, Karen A. Lillycrop, Mark H. Vickers, 12732 Quantitative characterization of cell synchronization Anthony B. Pleasants,