Journal Articles

  • Phenotypic comparisons of consensus variants versus laboratory resurrections of Precambrian proteins
    [Apr 2014]

    ABSTRACT

    Consensus-sequence engineering has generated protein variants with enhanced stability, and sometimes, with modulated biological function. Consensus mutations are often interpreted as the introduction of ancestral amino acid residues. However, the precise relationship between consensus engineering and ancestral protein resurrection is not fully understood. Here, we report the properties of proteins encoded by consensus sequences derived from a multiple sequence alignment of extant, class A β-lactamases, as compared with the properties of ancient Precambrian β-lactamases resurrected in the laboratory. These comparisons considered primary sequence, secondary, and tertiary structure, as well as stability and catalysis against different antibiotics. Out of the three consensus variants generated, one could not be expressed and purified (likely due to misfolding and/or low stability) and only one displayed substantial stability having substrate promiscuity, although to a lower extent than ancient β-lactamases. These results: (i) highlight the phenotypic differences between consensus variants and laboratory resurrections of ancestral proteins; (ii) question interpretations of consensus proteins as phenotypic proxies of ancestral proteins; and (iii) support the notion that ancient proteins provide a robust approach toward the preparation of protein variants having large numbers of mutational changes while possessing unique biomolecular properties. Proteins 2014. © 2014 Wiley Periodicals, Inc.

    Categories: Journal Articles
  • Essential function of the N-termini tails of the proteasome for the gating mechanism revealed by molecular dynamics simulations
    [Apr 2014]

    ABSTRACT

    Proteasome is involved in the degradation of proteins. Proteasome activators bind to the proteasome core particle (CP) and facilitate opening a gate of the CP, where Tyr8 and Asp9 in the N-termini tails of the CP form the ordered open gate. In a double mutant (Tyr8Gly/Asp9Gly), the N-termini tails are disordered and the stabilized open-gate conformation cannot be formed. To understand the gating mechanism of the CP for the translocation of the substrate, four different molecular dynamics simulations were carried out: ordered- and Tyr8Gly/Asp9Gly disordered-gate models of the CP complexed with an ATP-independent PA26 and ordered- and disordered-gate models of the CP complexed with an ATP-dependent PAN-like activator. The free-energies of the translocation of a polypeptide substrate moving through the gate were estimated. In the ordered-gate models, the substrate in the activator was more stable than that in the CP. The conformational entropy of the N-termini tails of the CP was larger when the substrate was in the activator than in the CP. In the disordered-gate models, the substrate in the activator was more destabilized than in the ordered-gate models. The mutated N-termini tails became randomized and their increased conformational entropy could no longer increase further even when the substrate was in the activator, meaning the randomized N-termini tails had lost the ability to stabilize the substrate in the activator. Thus, it was concluded that the dynamics of the N-termini tails entropically play a key role in the translocation of the substrate. Proteins 2014. © 2014 Wiley Periodicals, Inc.

    Categories: Journal Articles
  • Banding 2of NMR-derived methyl order parameters: Implications for protein dynamics
    [Apr 2014]

    ABSTRACT

    Our understanding of protein folding, stability, and function has begun to more explicitly incorporate dynamical aspects. Nuclear magnetic resonance has emerged as a powerful experimental method for obtaining comprehensive site-resolved insight into protein motion. It has been observed that methyl-group motion tends to cluster into three “classes” when expressed in terms of the popular Lipari-Szabo model-free squared generalized order parameter. Here the origins of the three classes or bands in the distribution of order parameters are examined. As a first step, a Bayesian based approach, which makes no a priori assumption about the existence or number of bands, is developed to detect the banding of values derived either from NMR experiments or molecular dynamics simulations. The analysis is applied to seven proteins with extensive molecular dynamics simulations of these proteins in explicit water to examine the relationship between O2 and fine details of the motion of methyl bearing side chains. All of the proteins studied display banding, with some subtle differences. We propose a very simple yet plausible physical mechanism for banding. Finally, our Bayesian method is used to analyze the measured distributions of methyl group motions in the catabolite activating protein and several of its mutants in various liganded states and discuss the functional implications of the observed banding to protein dynamics and function. Proteins 2014. © 2014 Wiley Periodicals, Inc.

    Categories: Journal Articles
  • Regio- and Stereoselective Intermolecular Oxidative Phenol Coupling in Streptomyces
    [Apr 2014]

    Journal of the American Chemical SocietyDOI: 10.1021/ja501630w
    Categories: Journal Articles
  • This Week in Science
    [Apr 2014]

    Patchy Insulation | Sleep Tight, Fly | Smoothing Graphene | On a Zeppelin | Starry Brightness | Changing Assemblages | Resilient Hyperpolarization | Hope for SUSY? | Strained Superconductor | Thin and Selective Outpourings | How Tight? | Resisting the Chop | Universal Immune Function | L[i]nc to Dendritic Cell Activation
    Categories: Journal Articles
  • [Editorial] Influenza and the Live Poultry Trade
    [Apr 2014]

    Live poultry trade at local markets has long been a part of China's national identity. From small villages to big cities, the gathering and selling of different birds in this vibrant atmosphere is at the heart of the country's cuisine culture. Unfortunately, the backdrop to this tradition has changed. Last year, the H7N9 virus, a new strain of influenza A, jumped from birds to humans, causing 144 cases of human infection and 47 deaths in China. Now a second wave of this flu is coursing through the country, with 258 confirmed cases and 99 deaths as of 8 April 2014. Scientific evidence points to a connection between the conditions at these live markets and the spread of flu, suggesting that until other means are found to prevent the transmission of or effectively treat the illness, China must shut down live poultry markets to prevent further spread of the virus and a possible global pandemic. Author: George F. Gao
    Categories: Journal Articles
  • Editors' Choice
    [Apr 2014]

    It's All in the Timing | Dead But Not Dangerous | Seeing Signaling | Disrupted Development | Doing Better Caged | On the Wall | Lead-Free Film
    Categories: Journal Articles
  • [News of the Week] This Week's Section
    [Apr 2014]

    Follow the links below for a roundup of the week's top stories in science, or download a PDF of the entire section. Around the WorldFindingsNewsmakersRandom Samples
    Categories: Journal Articles
  • [News of the Week] Around the World
    [Apr 2014]

    In science news around the world, the National Park Service decides not to introduce mainland wolves to rescue the declining wolf population on Lake Superior's Isle Royale, Japanese researchers plan to resume controversial whaling in 2015, Australia's Antarctic research program faces budget cuts, and more.
    Categories: Journal Articles
  • [News of the Week] Newsmakers
    [Apr 2014]

    Molecular biologist Feng Zhang wins the National Science Foundation's Alan T. Waterman Award for young researchers, President Barack Obama nominates White House budget office director Sylvia Mathews Burwell to replace outgoing Health and Human Services head Kathleen Sebelius, physicist Stuart Parkin wins the 2014 Millennium Technology Prize, and more.
    Categories: Journal Articles
  • [News of the Week] Random Sample
    [Apr 2014]

    The winners of the Science, Play and Research Kit Competition reimagine the childhood chemistry set—on a microfluidic chip.
    Categories: Journal Articles
  • Findings
    [Apr 2014]

    Hunter-Gatherers Don't Need Probiotics
    Categories: Journal Articles
  • [News & Analysis] U.S. Support for ITER Wavers as Costs Spiral
    [Apr 2014]

    Soaring cost estimates are jeopardizing the U.S. contribution to ITER, the massive international fusion energy project. Author: Adrian Cho
    Categories: Journal Articles
  • [News & Analysis] 'Humanized' Mouse Detects Deadly Drug Side Effects
    [Apr 2014]

    A chimeric mouse with a humanized liver offers a novel window into drug toxicity. Author: Jon Cohen
    Categories: Journal Articles
  • [News & Analysis] Ancient DNA Holds Clues to Gene Activity in Extinct Humans
    [Apr 2014]

    Researchers have harnessed the chemical degradation of fossil DNA to determine methylation patterns that may reveal which genes were turned on, or off, in ancient human species. Author: Elizabeth Pennisi
    Categories: Journal Articles
  • [News & Analysis] More Sophisticated Forecasts Yield Glimmer of Hope in Climate Gloom
    [Apr 2014]

    The latest Intergovernmental Panel on Climate Change report, on mitigating emissions, finds a few glimmers of hope amid gloomy projections. Author: Eli Kintisch
    Categories: Journal Articles
  • [News & Analysis] Almost-Earth Tantalizes Astronomers With Promise of Worlds to Come
    [Apr 2014]

    A new find from NASA's Kepler orbiting observatory is the first Earth-sized planet to be detected in the habitable zone of a star. Author: Yudhijit Bhattacharjee
    Categories: Journal Articles
  • Syndicate content