Different phenotypic outcome due to site-specific phosphorylation in the cancer-associated NQO1 enzyme studied by phosphomimetic mutations
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00564242" target="_blank" >RIV/61388971:_____/22:00564242 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/22:00564242 RIV/00216224:14740/22:00128774
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0003986122002764?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0003986122002764?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.abb.2022.109392" target="_blank" >10.1016/j.abb.2022.109392</a>
Alternative languages
Result language
angličtina
Original language name
Different phenotypic outcome due to site-specific phosphorylation in the cancer-associated NQO1 enzyme studied by phosphomimetic mutations
Original language description
Protein phosphorylation is a common phenomenon in human flavoproteins although the functional consequences of this site-specific modification are largely unknown. Here, we evaluated the effects of site-specific phosphorylation (using phosphomimetic mutations at sites S40, S82 and T128) on multiple functional aspects as well as in the structural stability of the antioxidant and disease-associated human flavoprotein NQO1 using biophysical and biochemical methods. In vitro biophysical studies revealed effects of phosphorylation at different sites such as decreased binding affinity for FAD and structural stability of its binding site (S82), conformational stability (S40 and S82) and reduced catalytic efficiency and functional cooperativity (T128). Local stability measurements by H/D exchange in different ligation states provided structural insight into these effects. Transfection of eukaryotic cells showed that phosphorylation at sites S40 and S82 may reduce steady-levels of NQO1 protein by enhanced proteasome-induced degradation. We show that site-specific phosphorylation of human NQO1 may cause pleiotropic and counterintuitive effects on this multifunctional protein with potential implications for its relationships with human disease. Our approach allows to establish relationships between site-specific phosphorylation, functional and structural stability effects in vitro and inside cells paving the way for more detailed analyses of phosphorylation at the flavoproteome scale.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/ED1.1.00%2F02.0109" target="_blank" >ED1.1.00/02.0109: Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Archives of Biochemistry and Biophysics
ISSN
0003-9861
e-ISSN
1096-0384
Volume of the periodical
729
Issue of the periodical within the volume
OCT 30 2022
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
109392
UT code for WoS article
000867178000002
EID of the result in the Scopus database
2-s2.0-85137903560