Allosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00564248" target="_blank" >RIV/61388971:_____/22:00564248 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/22:10444668 RIV/00216224:14740/22:00128776
Result on the web
<a href="https://www.mdpi.com/2076-3921/11/6/1110" target="_blank" >https://www.mdpi.com/2076-3921/11/6/1110</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/antiox11061110" target="_blank" >10.3390/antiox11061110</a>
Alternative languages
Result language
angličtina
Original language name
Allosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations
Original language description
Allosterism is a common phenomenon in protein biochemistry that allows rapid regulation of protein stability, dynamics and function. However, the mechanisms by which allosterism occurs (by mutations or post-translational modifications (PTMs)) may be complex, particularly due to long-range propagation of the perturbation across protein structures. In this work, we have investigated allosteric communication in the multifunctional, cancer-related and antioxidant protein NQO1 by mutating several fully buried leucine residues (L7, L10 and L30) to smaller residues (V, A and G) at sites in the N-terminal domain. In almost all cases, mutated residues were not close to the FAD or the active site. Mutations L> G strongly compromised conformational stability and solubility, and L30A and L30V also notably decreased solubility. The mutation L10A, closer to the FAD binding site, severely decreased FAD binding affinity (approximate to 20 fold vs. WT) through long-range and context-dependent effects. Using a combination of experimental and computational analyses, we show that most of the effects are found in the apo state of the protein, in contrast to other common polymorphisms and PTMs previously characterized in NQO1. The integrated study presented here is a first step towards a detailed structural-functional mapping of the mutational landscape of NQO1, a multifunctional and redox signaling protein of high biomedical relevance.
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
Antioxidants
ISSN
2076-3921
e-ISSN
2076-3921
Volume of the periodical
11
Issue of the periodical within the volume
6
Country of publishing house
CH - SWITZERLAND
Number of pages
16
Pages from-to
1110
UT code for WoS article
000816602700001
EID of the result in the Scopus database
2-s2.0-85131635705