Comparative structural analysis of 1-methyladenosine, 7-methylguanosine, ethenoadenosine and their protonated salts IV:¹H,¹³C, and¹⁵N NMR studies at natural isotope abundance

Abstract

The 1H, 13C, and 15N NMR spectra of neutral and protonated forms of the nucleosides 1-methyladenosine (m1A), 7-methylguanosine (m7G) and ethenoadenosine (EA), as a model compound, have been analyzed in order to assign the site of protonation in m1A and m7G. Protonation of these nucleosides occurs in the pyrimidine ring of m1A and EA and in the imidazole ring of m7G, with the charge being distributed rather than localized. Structural differences for both m1A and m7G were observed in solution and compared with those existing in the crystal state of monomers as well as in tRNA where these nucleosides occur quite often. The protonated nucleoside structures in solution compared favorably in sugar pucker and glycosidic bond conformations with x-ray crystallographic data. Methyl group carbon chemical shifts of the protonated mononucleosides corresponded to those of the methyls of the respective nucleosides in native tRNA structures. Therefore, the tRNA methyl group carbon chemical shifts are indicative of fully protonated nucleosides in the native, three dimensional structure of the nucleic acid.

Additive CHARMM force field for naturally occurring modified ribonucleotides

“…The methylation on N7 results in a positively charged purine ring and makes N1 more acidic. Although m 7 G has been found to have both protonated (keto) and deprotonated (enol) zwitterionic states, its biochemical functions are mostly related to the protonated state . Furthermore, a positively charged m 7 G keeps the same configuration as guanine, in contrast to the N1 deprotonated state, so that hydrogen bonding and stacking patterns in tRNA are not disturbed .…”

Complete Modification Maps for the Cytosolic Small and Large Subunit rRNAs of Euglena gracilis: Functional and Evolutionary Implications of Contrasting Patterns between the Two rRNA Components

“…The unusual cluster of m 1 A residues at LSU rRNA positions 1863, 1864, 1866, 1868, and 1869 also caused blurred C bands in chemical sequencing gels. The positive charge on m 1 A (and m 7 G) 33 explains the unusually large band spacing in sequencing gels.…”

Characterization of the Posttranscriptional Modifications in Legionella pneumophila Small‐Subunit Ribosomal RNA

“…m 7 G at Position 527 in the 530 Loop in Helix 18. 7-Methylation has profound influence on the electron distribution of the guanine base (at physiological pH, a zwitterion is formed [22]). Studies on tRNA indicate that, in tertiary RNA structure, this nucleoside is protonated by tertiary H-bonding, making it positively charged.…”