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Crystal structure of Mycobacterium tuberculosis O-6-methylguanine-DNA methyltransferase protein clusters assembled on to damaged DNA
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SYSNO ASEP 0469556 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Crystal structure of Mycobacterium tuberculosis O-6-methylguanine-DNA methyltransferase protein clusters assembled on to damaged DNA Tvůrce(i) Miggiano, R. (IT)
Perugino, G. (IT)
Ciaramella, M. (IT)
Serpe, M. (IT)
Rejman, Dominik (UOCHB-X) RID, ORCID
Páv, Ondřej (UOCHB-X) RID, ORCID
Pohl, Radek (UOCHB-X) RID, ORCID
Garavaglia, S. (IT)
Lahiri, S. (IT)
Rizzi, M. (IT)
Rossi, F. (IT)Zdroj.dok. Biochemical Journal. - : Portland Press - ISSN 0264-6021
Roč. 473, č. 2 (2016), s. 123-133Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova DNA repair ; DNA-binding protein ; Mycobacterium tuberculosis ; O-6-methylguanine-DNA methyltransferase ; co-operativity ; crystal structure Vědní obor RIV CE - Biochemie Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000374784300003 EID SCOPUS 84955461156 DOI https://doi.org/10.1042/BJ20150833 Anotace Mycobacterium tuberculosis O-6-methylguanine-DNA methyltransferase (MtOGT) contributes to protect the bacterial GC-rich genome against the pro-mutagenic potential of O-6-methylated guanine in DNA. Several strains of M. tuberculosis found worldwide encode a point-mutated O-6-methylguanine-DNA methyltransferase (OGT) variant (MtOGT-R37L), which displays an arginine-to-leucine substitution at position 37 of the poorly functionally characterized N-terminal domain of the protein. Although the impact of this mutation on the MtOGT activity has not yet been proved in vivo, we previously demonstrated that a recombinant MtOGT-R37L variant performs a suboptimal alkylated-DNA repair in vitro, suggesting a direct role for the Arg(37)-bearing region in catalysis. The crystal structure of MtOGT complexed with modified DNA solved in the present study reveals details of the protein-protein and protein-DNA interactions occurring during alkylated-DNA binding, and the protein capability also to host unmodified bases inside the active site, in a fully extrahelical conformation. Our data provide the first experimental picture at the atomic level of a possible mode of assembling three adjacent MtOGT monomers on the same monoalkylated dsDNA molecule, and disclose the conformational flexibility of discrete regions of MtOGT, including the Arg(37)-bearing random coil. This peculiar structural plasticity of MtOGT could be instrumental to proper protein clustering at damaged DNA sites, as well as to protein-DNA complexes disassembling on repair. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2017
Počet záznamů: 1