Temperature-Induced Replacement of Phosphate Proton with Metal Ion Captured in Neutron Structures of A-DNA

Venu Gopal Vandavasi, Matthew P. Blakeley, David A. Keen, Lillian R. Hu, Zhen Huang, Andrey Kovalevsky

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Nucleic acids can fold into well-defined 3D structures that help determine their function. Knowing precise nucleic acid structures can also be used for the design of nucleic acid-based therapeutics. However, locations of hydrogen atoms, which are key players of nucleic acid function, are normally not determined with X-ray crystallography. Accurate determination of hydrogen atom positions can provide indispensable information on protonation states, hydrogen bonding, and water architecture in nucleic acids. Here, we used neutron crystallography in combination with X-ray diffraction to obtain joint X-ray/neutron structures at both room and cryo temperatures of a self-complementary A-DNA oligonucleotide d[GTGG(C Se )CAC] 2 containing 2′-SeCH 3 modification on Cyt5 (C Se ) at pH 5.6. We directly observed protonation of a backbone phosphate oxygen of Ade7 at room temperature. The proton is replaced with hydrated Mg 2+ upon cooling the crystal to 100 K, indicating that metal binding is favored at low temperature, whereas proton binding is dominant at room temperature.

Original languageEnglish
Pages (from-to)1645-1650.e3
JournalStructure
Volume26
Issue number12
DOIs
StatePublished - Dec 4 2018

Funding

This research at ORNL's High Flux Isotope Reactor (IMAGINE beamline) was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy (DOE). The authors thank Institut Laue Langevin (beamline LADI-III) for awarded neutron beamtime. Notice: This manuscript has been authored by UT-Battelle under DOE contract no. DE-AC05-00OR22725. This work was supported by the ORNL Laboratory Directed Research and Development grant to A.K. and by NIH ( R01GM095881 and R42ES026935 ) to Z.H.; and the US Department of Energy 's Office of Basic Energy Sciences.

FundersFunder number
Office of Basic Energy Sciences
Scientific User Facilities Division
US Department of Energy
UT-Battelle
National Institutes of HealthR01GM095881
U.S. Department of Energy
National Institute of Environmental Health SciencesR42ES026935
Laboratory Directed Research and Development

    Keywords

    • A-form DNA
    • RNA
    • hydrogen bonding
    • metal binding
    • neutron crystallography
    • oligonucleotide crystallization
    • protonation
    • selenium modification and derivatization

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