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  • 1
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    Springer Nature
    In: Nature
    Publication Date: 2019
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2019
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2016-05-19
    Description: An irradiated brown-dwarf companion to an accreting white dwarf Nature 533, 7603 (2016). doi:10.1038/nature17952 Authors: Juan V. Hernández Santisteban, Christian Knigge, Stuart P. Littlefair, Rene P. Breton, Vikram S. Dhillon, Boris T. Gänsicke, Thomas R. Marsh, Magaretha L. Pretorius, John Southworth & Peter H. Hauschildt Interacting compact binary systems provide a natural laboratory in which to study irradiated substellar objects. As the mass-losing secondary (donor) in these systems makes a transition from the stellar to the substellar regime, it is also irradiated by the primary (compact accretor). The internal and external energy fluxes are both expected to be comparable in these objects, providing access to an unexplored irradiation regime. The atmospheric properties of donors are largely unknown, but could be modified by the irradiation. To constrain models of donor atmospheres, it is necessary to obtain accurate observational estimates of their physical properties (masses, radii, temperatures and albedos). Here we report the spectroscopic detection and characterization of an irradiated substellar donor in an accreting white-dwarf binary system. Our near-infrared observations allow us to determine a model-independent mass estimate for the donor of 0.055 ± 0.008 solar masses and an average spectral type of L1 ± 1, supporting both theoretical predictions and model-dependent observational constraints that suggest that the donor is a brown dwarf. Our time-resolved data also allow us to estimate the average irradiation-induced temperature difference between the dayside and nightside of the substellar donor (57 kelvin) and the maximum difference between the hottest and coolest parts of its surface (200 kelvin). The observations are well described by a simple geometric reprocessing model with a bolometric (Bond) albedo of less than 0.54 at the 2σ confidence level, consistent with high reprocessing efficiency, but poor lateral heat redistribution in the atmosphere of the brown-dwarf donor. These results add to our knowledge of binary evolution, in that the donor has survived the transition from the stellar to the substellar regime, and of substellar atmospheres, in that we have been able to test a regime in which the irradiation and the internal energy of a brown dwarf are comparable.
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-04-28
    Description: The pentadehydro-Diels–Alder reaction Nature 532, 7600 (2016). doi:10.1038/nature17429 Authors: Teng Wang, Rajasekhar Reddy Naredla, Severin K. Thompson & Thomas R. Hoye In the classic Diels–Alder [4 + 2] cycloaddition reaction, the overall degree of unsaturation (or oxidation state) of the 4π (diene) and 2π (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic Diels–Alder reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the number of hydrogen atoms in the reactant pair and in the resulting product is reduced by, for example, four in the tetradehydro-Diels–Alder (TDDA) and by six in the hexadehydro-Diels–Alder (HDDA) reactions. Any oxidation state higher than tetradehydro (that is, lacking more than four hydrogens) leads to the production of a reactive intermediate that is more highly oxidized than benzene. This increases the power of the overall process substantially, because trapping of the reactive intermediate can be used to increase the structural complexity of the final product in a controllable and versatile manner. Here we report an unprecedented overall 4π + 2π cycloaddition reaction that generates a different, highly reactive intermediate known as an α,3-dehydrotoluene. This species is in the same oxidation state as a benzyne. Like benzynes, α,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization process a pentadehydro-Diels–Alder (PDDA) reaction—a nomenclature chosen for chemical taxonomic reasons rather than mechanistic ones. In addition to alkynes, nitriles (RC≡N), although non-participants in aza-HDDA reactions, readily function as the 2π component in PDDA cyclizations to produce, via trapping of the α,3-(5-aza)dehydrotoluene intermediates, pyridine-containing products.
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2016-09-29
    Description: Directed evolution of artificial metalloenzymes for in vivo metathesis Nature 537, 7622 (2016). doi:10.1038/nature19114 Authors: Markus Jeschek, Raphael Reuter, Tillmann Heinisch, Christian Trindler, Juliane Klehr, Sven Panke & Thomas R. Ward The field of biocatalysis has advanced from harnessing natural enzymes to using directed evolution to obtain new biocatalysts with tailor-made functions. Several tools have recently been developed to expand the natural enzymatic repertoire with abiotic reactions. For example, artificial metalloenzymes, which combine the versatile reaction scope of transition metals with the beneficial catalytic features of enzymes, offer an attractive means to engineer new reactions. Three complementary strategies exist: repurposing natural metalloenzymes for abiotic transformations; in silico metalloenzyme (re-)design; and incorporation of abiotic cofactors into proteins. The third strategy offers the opportunity to design a wide variety of artificial metalloenzymes for non-natural reactions. However, many metal cofactors are inhibited by cellular components and therefore require purification of the scaffold protein. This limits the throughput of genetic optimization schemes applied to artificial metalloenzymes and their applicability in vivo to expand natural metabolism. Here we report the compartmentalization and in vivo evolution of an artificial metalloenzyme for olefin metathesis, which represents an archetypal organometallic reaction without equivalent in nature. Building on previous work on an artificial metallohydrolase, we exploit the periplasm of Escherichia coli as a reaction compartment for the ‘metathase’ because it offers an auspicious environment for artificial metalloenzymes, mainly owing to low concentrations of inhibitors such as glutathione, which has recently been identified as a major inhibitor. This strategy facilitated the assembly of a functional metathase in vivo and its directed evolution with substantially increased throughput compared to conventional approaches that rely on purified protein variants. The evolved metathase compares favourably with commercial catalysts, shows activity for different metathesis substrates and can be further evolved in different directions by adjusting the workflow. Our results represent the systematic implementation and evolution of an artificial metalloenzyme that catalyses an abiotic reaction in vivo, with potential applications in, for example, non-natural metabolism.
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2017-05-11
    Description: Core Mediator structure at 3.4 Å extends model of transcription initiation complex Nature 545, 7653 (2017). doi:10.1038/nature22328 Authors: Kayo Nozawa, Thomas R. Schneider & Patrick Cramer Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution. The structure shows an unaltered head module, and reveals the intricate middle module, which we show is globally required for transcription. Sites of known Mediator mutations cluster at the interface between the head and middle modules, and in terminal regions of the head subunits Med6 (ref. 16) and Med17 (ref. 17) that tether the middle module. The structure led to a model for Saccharomyces cerevisiae cMed that could be combined with the 3.6 Å cryo-electron microscopy structure of the core PIC (cPIC). The resulting atomic model of the cPIC–cMed complex informs on interactions of the submodules forming the middle module, called beam, knob, plank, connector, and hook. The hook is flexibly linked to Mediator by a conserved hinge and contacts the transcription initiation factor IIH (TFIIH) kinase that phosphorylates the carboxy (C)-terminal domain (CTD) of Pol II and was recently positioned on the PIC. The hook also contains residues that crosslink to the CTD and reside in a previously described cradle. These results provide a framework for understanding Mediator function, including its role in stimulating CTD phosphorylation by TFIIH.
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Springer Nature
    In: Nature
    Publication Date: 2017-05-04
    Description: Nomenclature: Share names for dinosaur divisions Nature 545, 7652 (2017). doi:10.1038/545030d Author: Thomas R. Holtz Matthew Baron and colleagues propose a radical revision of dinosaur relationships (Nature543, 501–506; 2017). I suggest that borrowing from the field's rich history could help to prevent unnecessary confusion.Historically, Saurischia is one of the two basic divisions
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2019
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 10
    Publication Date: 2020-07-29
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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