title: Benchmark Theoretical and Experimental Study on (15)N NMR Shifts of Oxidatively Damaged Guanine.
abstract: The (15)N NMR shifts of 9-ethyl-8-oxoguanine (OG) were calculated and measured in liquid DMSO and in crystal. The OG molecule is a model for oxidatively damaged 2'-deoxyguanosine that occurs owing to oxidative stress in cell. The DNA lesion is repaired with human 8-oxoguanine glycosylase 1 (hOGG1) base-excision repair enzyme, however, the exact mechanism of excision of damaged nucleobase with hOGG1 is currently unknown. This benchmark study on (15)N NMR shifts of OG aims their accurate structural interpretation and calibration of the calculation protocol utilizable in future studies on mechanism of hOGG1 enzyme. The effects of NMR reference, DFT functional, basis set, solvent, structure, and dynamics on calculated (15)N NMR shifts were first evaluated for OG in crystal to calibrate the best performing calculation method. The effect of large-amplitude motions on (15)N NMR shifts of OG in liquid was calculated employing molecular dynamics. The B3LYP method with Iglo-III basis used for B3LYP optimized geometry with 6-311++G(d,p) basis and including effects of solvent and molecular dynamic was the calculation protocol used for calculation of (15)N NMR shifts of OG. The NMR shift of N9 nitrogen of OG was particularly studied because the atom is involved in an N-glycosidic bond that is cleaved with hOGG1. The change of N9 NMR shift owing to oxidation of 9-ethylguanine (G) measured in liquid was -27.1 ppm. The calculated N9 NMR shift of OG deviated from experiment in crystal and in liquid by 0.45 and 0.65 ppm, respectively. The calculated change of N9 NMR shift owing to notable N9-pyramidalization of OG in one previously found polymorph was 20.53 ppm. We therefore assume that the pyramidal geometry of N9 nitrogen that could occur for damaged DNA within hOGG1 catalytic site might be detectable with (15)N NMR spectroscopy. The calculation protocol can be used for accurate structural interpretation of (15)N NMR shifts of oxidatively damaged guanine DNA residue.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Dračínský
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Šála
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Klepetářová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.|Institute of Physics, Academy of Sciences of the Czech Republic , v.v.i, Na Slovance 2, CZ-182 21 Prague 8, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Šebera
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Fukal
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Holečková
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University , 180 Nishihama-Boji, Yamashirocho, Tokushima, Tokushima 980-8578, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Nencka
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i. , Flemingovo náměstí 2, 16610 Praha, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Sychrovský
mesh_terms: D018360:Crystallography, X-Ray; D006147:Guanine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D056004:Molecular Dynamics Simulation; D018384:Oxidative Stress
chemical_list: D006147:Guanine