The mechanism of the glycosylase reaction with hOGG1 base-excision repair enzyme: concerted effect of Lys249 and Asp268 during excision of 8-oxoguanine
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00475942" target="_blank" >RIV/61388963:_____/17:00475942 - isvavai.cz</a>
Alternative codes found
RIV/61388971:_____/17:00475942 RIV/68407700:21230/17:00315473
Result on the web
<a href="https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx157" target="_blank" >https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx157</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkx157" target="_blank" >10.1093/nar/gkx157</a>
Alternative languages
Result language
angličtina
Original language name
The mechanism of the glycosylase reaction with hOGG1 base-excision repair enzyme: concerted effect of Lys249 and Asp268 during excision of 8-oxoguanine
Original language description
The excision of 8-oxoguanine (oxoG) by the human 8-oxoguanine DNA glycosylase 1 (hOGG1) base-excision repair enzyme was studied by using the QM/MM (M06-2X/6-31G(d,p): OPLS2005) calculation method and nuclear magnetic resonance (NMR) spectroscopy. The calculated glycosylase reaction included excision of the oxoG base, formation of Lys249-ribose enzyme-substrate covalent adduct and formation of a Schiff base. The formation of a Schiff base with Delta G(#) = 17.7 kcal/mol was the rate-limiting step of the reaction. The excision of the oxoG base with Delta G(#) = 16.1 kcal/mol proceeded via substitution of the C1'-N9 N-glycosidic bond with an H-N9 bond where the negative charge on the oxoG base and the positive charge on the ribose were compensated in a concerted manner by NH3+(Lys249) and CO2- (Asp268), respectively. The effect of Asp268 on the oxoG excision was demonstrated with H-1 NMR for WT hOGG1 and the hOGG1(D268N) mutant: the excision of oxoG was notably suppressed when Asp268 was mutated to Asn. The loss of the base-excision function was rationalized with QM/MM calculations and Asp268 was confirmed as the electrostatic stabilizer of ribose oxocarbenium through the initial base-excision step of DNA repair. The NMR experiments and QM/MM calculations consistently illustrated the base-excision reaction operated by hOGG1.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
<a href="/en/project/GA13-27676S" target="_blank" >GA13-27676S: Pyramidalization of the glycosidic nitrogen in nucleic acids; linking the structural phenomenon with chemistry of N-glycosidic bond cleavage</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
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Volume of the periodical
45
Issue of the periodical within the volume
9
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
5231-5242
UT code for WoS article
000402064200028
EID of the result in the Scopus database
2-s2.0-85027274090