Pyramidalization of the Glycosidic Nitrogen Provides the Way for Efficient Cleavage of the N-Glycosidic Bond of 8-OxoG with the hOGG1 DNA Repair Protein

0382846 - ÚOCHB 2013 RIV US eng J - Journal Article
Šebera, Jakub - Trantírek, L. - Tanaka, Y. - Sychrovský, Vladimír
Pyramidalization of the Glycosidic Nitrogen Provides the Way for Efficient Cleavage of the N-Glycosidic Bond of 8-OxoG with the hOGG1 DNA Repair Protein.
Journal of Physical Chemistry B. Roč. 116, č. 41 (2012), s. 12535-12544. ISSN 1520-6106. E-ISSN 1520-5207
R&D Projects: GA ČR GAP205/10/0228
Grant - others:AV ČR(CZ) M200551205
Institutional research plan: CEZ:AV0Z40550506
Keywords : hOGG1 enzyme * DFT * glycosidic bond cleavage
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 3.607, year: 2012

A mechanistic pathway for cleavage of the N-glycosidic bond of 8-oxo-2′-deoxyguanosine (oxoG) catalyzed with the human 8-oxoguanine glycosylase 1 DNA repair protein (hOGG1) is proposed in this theoretical study. The reaction scheme suggests direct proton addition to the glycosidic nitrogen N9 of oxoG from the Nε-ammonium of Lys249 residue of hOGG1 that is enabled owing to the N9 pyramidal geometry. The modification of aromatic character introduced by oxidation to the nucleobase thus seems to be the factor that is checked by hOGG1 to achieve base-specific cleavage.
Permanent Link: http://hdl.handle.net/11104/0007200