eprintid: 10099376 rev_number: 15 eprint_status: archive userid: 608 dir: disk0/10/09/93/76 datestamp: 2020-06-03 14:24:41 lastmod: 2021-10-03 23:59:21 status_changed: 2020-06-03 14:24:41 type: article metadata_visibility: show creators_name: Zhang, Y creators_name: El Omari, K creators_name: Duman, R creators_name: Liu, S creators_name: Haider, S creators_name: Wagner, A creators_name: Parkinson, GN creators_name: Wei, D title: Native de novo structural determinations of non-canonical nucleic acid motifs by X-ray crystallography at long wavelengths ispublished: inpress divisions: UCL divisions: B02 divisions: C08 divisions: D10 divisions: G09 note: © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/). abstract: Obtaining phase information remains a formidable challenge for nucleic acid structure determination. The introduction of an X-ray synchrotron beamline designed to be tunable to long wavelengths at Diamond Light Source has opened the possibility to native de novo structure determinations by the use of intrinsic scattering elements. This provides opportunities to overcome the limitations of introducing modifying nucleotides, often required to derive phasing information. In this paper, we build on established methods to generate new tools for nucleic acid structure determinations. We report on the use of (i) native intrinsic potassium single-wavelength anomalous dispersion methods (K-SAD), (ii) use of anomalous scattering elements integral to the crystallization buffer (extrinsic cobalt and intrinsic potassium ions), (iii) extrinsic bromine and intrinsic phosphorus SAD to solve complex nucleic acid structures. Using the reported methods we solved the structures of (i) Pseudorabies virus (PRV) RNA G-quadruplex and ligand complex, (ii) PRV DNA G-quadruplex, and (iii) an i-motif of human telomeric sequence. Our results highlight the utility of using intrinsic scattering as a pathway to solve and determine non-canonical nucleic acid motifs and reveal the variability of topology, influence of ligand binding, and glycosidic angle rearrangements seen between RNA and DNA G-quadruplexes of the same sequence. date: 2020-05-26 date_type: published official_url: https://doi.org/10.1093/nar/gkaa439 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1786775 doi: 10.1093/nar/gkaa439 pii: 5846030 lyricists_name: Parkinson, Gary lyricists_name: Shozeb, Syed lyricists_id: GNPAR11 lyricists_id: SMSSH06 actors_name: Kalinowski, Damian actors_id: DKALI47 actors_role: owner full_text_status: public publication: Nucleic Acids Research event_location: England issn: 0305-1048 citation: Zhang, Y; El Omari, K; Duman, R; Liu, S; Haider, S; Wagner, A; Parkinson, GN; Zhang, Y; El Omari, K; Duman, R; Liu, S; Haider, S; Wagner, A; Parkinson, GN; Wei, D; - view fewer <#> (2020) Native de novo structural determinations of non-canonical nucleic acid motifs by X-ray crystallography at long wavelengths. Nucleic Acids Research 10.1093/nar/gkaa439 <https://doi.org/10.1093/nar%2Fgkaa439>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10099376/1/Parkinson_Native%20de%20novo%20structural%20determinations%20of%20non-canonical%20nucleic%20acid%20motifs%20by%20X-ray%20crystallography%20at%20long%20wavelengths_AOP.pdf