1,722,919 research outputs found

    Ribozyme catalysis with a twist: active state of the twister ribozyme in solution predicted from molecular simulation

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    We present results from molecular dynamics simulations and free energy calculations of the twister ribozyme at different stages along the reaction path to gain insight into its mechanism. The results, together with recent biochemical experiments, provide support for a mechanism involving general-acid catalysis by a conserved adenine residue in the active site. Although adenine has been previously implicated as a general acid acting through the N1 position in other ribozymes such as the hairpin and VS ribozymes, in the twister ribozyme there may be a twist. Biochemical experiments suggest that general acid catalysis may occur through the N3 position, which has never before been implicated in this role; however, currently, there is a lack of a detailed structural model for the active state of the twister ribozyme in solution that is consistent with these and other experiments. Simulations in a crystalline environment reported here are consistent with X-ray crystallographic data, and suggest that crystal packing contacts trap the RNA in an inactive conformation with U-1 in an extruded state that is incompatible with an in-line attack to the scissile phosphate. Simulations in solution, on the other hand, reveal this region to be dynamic and able to adopt a conformation where U-1 is stacked with G33. In this state, the nucleophile is in line with the scissile phosphate, and the N1 position of G33 and N3 position of A1 are poised to act as a general base and acid, respectively, as supported by mutational experiments. Free energy calculations further predict the electrostatic environment causes a shift of the microscopic pKa at the N3 position of A1 toward neutrality by approximately 5 pKa units. These results offer a unified interpretation of a broad range of currently available experimental data that points to a novel mode of general acid catalysis through the N3 position of an adenine nucleobase, thus expanding the repertoire of known mechanistic strategies employed by small nucleolytic ribozymes.Peer reviewe

    Colin S. Moffat

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    Portrait photograph of Colin S. Moffat.For more information on Colin S. Moffat, see https://springfield.as.atlas-sys.com/agents/people/825

    Davies, Colin S, NX26806

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    This record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/380759Surname: DAVIES Given Name(s) or Initials: COLIN S Military Service Number or Last Known Location: NX26806 Missing, Wounded and Prisoner of War Enquiry Card Index Number: 22207195457 Item: [2016.0049.13052] "Davies, Colin S, NX26806

    On “The Grand Strategic Thought of Colin S. Gray” and Author\u27s Response

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    This commentary responds to Lukas Milevski’s article, “The Grand Strategic Thought of Colin S. Gray,” published in the Winter 2021–22 issue of Parameters (vol. 51, no. 4)

    Dant, Colin S, [No Service Number]

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    This record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/380490Surname: DANT Given Name(s) or Initials: COLIN S Military Service Number or Last Known Location: No Service Number Missing, Wounded and Prisoner of War Enquiry Card Index Number: 47966194302 Item: [2016.0049.12783] "Dant, Colin S, [No Service Number]

    Reed College President Colin S. Diver, 2002

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    https://rdc.reed.edu/v1/resources/b7ef6af9-c234-4807-ad8f-b1cca7e2072a/thumb/128.jpgPortrait of Reed College President Colin S. Diver when he started at Reed in 2002

    Reed President Colin S. Diver, 2010

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    https://rdc.reed.edu/v1/resources/c93fce71-c10c-4dca-a7dd-46c0088dd634/thumb/128.jpgReed College President Colin S. Diver, standing on the porch at the east end of Eliot Hall, July 10, 2010

    Colin S. Gray. Strategic Studies. A Critical Assesment

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    Coutau-Bégarie Hervé. Colin S. Gray. Strategic Studies. A Critical Assesment. In: Politique étrangère, n°2 - 1983 - 48ᵉannée. pp. 485-486

    Colin S. Gray. Strategic Studies. A Critical Assesment

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    Coutau-Bégarie Hervé. Colin S. Gray. Strategic Studies. A Critical Assesment. In: Politique étrangère, n°2 - 1983 - 48ᵉannée. pp. 485-486
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