title: Mg2+ ions: do they bind to nucleobase nitrogens?
abstract: Given the many roles proposed for Mg2+in nucleic acids, it is essential to accurately determine their binding modes. Here, we surveyed the PDB to classify Mg2+inner-sphere binding patterns to nucleobase imine N1/N3/N7 atoms. Among those, purine N7 atoms are considered to be the best nucleobase binding sites for divalent metals. Further, Mg2+coordination to N7 has been implied in several ribozyme catalytic mechanisms. We report that Mg2+assigned near imine nitrogens derive mostly from poor interpretations of electron density patterns and are most often misidentified Na+, K+, NH4+ions, water molecules or spurious density peaks. Consequently, apart from few documented exceptions, Mg2+ions do not bind to N7 atoms. Without much of a surprise, Mn2+, Zn2+and Cd2+, which have a higher affinity for nitrogens, may contact N7 atoms when present in crystallization buffers. In this respect, we describe for the first time a potential Zn2+ribosomal binding site involving two purine N7 atoms. Further, we provide a set of guidelines to help in the assignment of Mg2+in crystallographic, cryo-EM, NMR and model building practices and discuss implications of our findings related to ion substitution experiments.
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, F-67000 Strasbourg, France.|Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Leonarski
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, F-67000 Strasbourg, France.
authors.forename: Luigi
authors.initials: L
authors.lastname: D'Ascenzo
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, F-67000 Strasbourg, France p.auffinger@ibmc-cnrs.unistra.fr.
authors.forename: Pascal
authors.identifier: 0000-0002-3816-2721
authors.initials: P
authors.lastname: Auffinger
mesh_terms: D002413:Cations, Divalent / Q000737:chemistry*; D002414:Cations, Monovalent / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry; D012997:Solvents
chemical_list: D002413:Cations, Divalent; D002414:Cations, Monovalent; D009696:Nucleic Acids; D012997:Solvents; D008274:Magnesium; D009584:Nitrogen; D010100:Oxygen