Počet záznamů: 1
Allosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations
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SYSNO ASEP 0564248 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Allosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations Tvůrce(i) Pacheco-Garcia, J. L. (ES)
Loginov, Dmitry Sergej (MBU-M) RID
Anoz-Carbonell, E. (ES)
Vaňková, Pavla (MBU-M) ORCID
Palomino-Morales, R. (ES)
Salido, E. (ES)
Man, Petr (MBU-M) RID, ORCID
Medina, M. (ES)
Naganathan, A. N. (IN)
Pey, Angel L. (ES)Číslo článku 1110 Zdroj.dok. Antioxidants. - : MDPI
Roč. 11, č. 6 (2022)Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova antioxidant defense ; flavoprotein ; FAD binding ; structural perturbation ; protein core ; allosterism ; cavity-making mutation Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology Vědní obor RIV – spolupráce Biotechnologický ústav CEP ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Výzkumná infrastruktura CIISB II - 90127 - Masarykova univerzita Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 ; BTO-N - RVO:86652036 UT WOS 000816602700001 EID SCOPUS 85131635705 DOI 10.3390/antiox11061110 Anotace 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. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2023 Elektronická adresa https://www.mdpi.com/2076-3921/11/6/1110
Počet záznamů: 1