Počet záznamů: 1
The activation of N-glycosidic bond cleavage performed by base-excision repair enzyme hOGG1; Theoretical study of the role of Lys 249 residue in activation of G, OxoG and FapyG
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SYSNO ASEP 0435412 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The activation of N-glycosidic bond cleavage performed by base-excision repair enzyme hOGG1; Theoretical study of the role of Lys 249 residue in activation of G, OxoG and FapyG Tvůrce(i) Šebera, Jakub (UOCHB-X) RID, ORCID
Trantírek, L. (CZ)
Tanaka, Y. (JP)
Nencka, Radim (UOCHB-X) RID, ORCID
Fukal, J. (CZ)
Sychrovský, Vladimír (UOCHB-X) RID, ORCIDCelkový počet autorů 6 Zdroj.dok. RSC Advances. - : Royal Society of Chemistry - ISSN 2046-2069
Roč. 4, č. 83 (2014), s. 44043-44051Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova DFT ; QM/MM ; Fukui indices ; hOGG1 ; aromaticity ; 8-OxoG Vědní obor RIV CF - Fyzikální chemie a teoretická chemie CEP GA13-27676S GA ČR - Grantová agentura ČR Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000344527300030 EID SCOPUS 84907611568 DOI https://doi.org/10.1039/c4ra08278h Anotace The activation of N-glycosidic bond cleavage performed by the lysine 249 (Lys 249) residue of base-excision repair enzyme hOGG1 was calculated for 2'-deoxyguanosine (G), 8-oxo-2'-deoxyguanosine (OxoG) and N6-(2'-beta-D-deoxyribofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). The interaction sites of Lys 249 included the C1', N3, and N9 atoms of the nucleosides. The N9-pathway, specifically the attack of lone-pair electrons of glycosidic nitrogen N9 of a nucleoside on the proton of the N epsilon-ammonium group of Lys 249, resulted in effective activation of the C1'-N9 bond that was highly specific with respect to normal (G) and damaged (OxoG, FapyG) nucleosides. The specificity of the N9-pathway was because of the electrophilic (G) or nucleophilic (OxoG, FapyG) character of the glycosidic nitrogen and because of the specific interactions of the residues within the catalytic pocket with the substrate (particularly the Gly 42 hOGG1 residue) that enforced the displacement of G out of the interaction range of Lys 249. The chemical modifications of G owing to damage specifically affected a number of molecular properties, particularly the electrophilicity/nucleophilicity of N9 and the C1'-N9 bond order and the aromatic character of the nucleobases. The N9-pathway could be involved as a check-point mechanism during base-excision performed by hOGG1. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2015
Počet záznamů: 1