Structural and functional studies of coronaviral RNA-methyltransferases

0567310 - ÚOCHB 2023 RIV CZ eng A - Abstrakt
Bouřa, Evžen
Structural and functional studies of coronaviral RNA-methyltransferases.
Czech Chemical Society Symposium Series. Roč. 20, č. 6 (2022), s. 352-352. ISSN 2336-7202.
[Annual meeting of the National Institute of Virology and Bacteriology (NIVB) /1./. 30.11.2022-02.12.2022, Kutná Hora]
Grant CEP: GA MŠMT(CZ) LX22NPO5103
Institucionální podpora: RVO:61388963
Klíčová slova: RNA-methyltransferase * antiviral * coronavirus
Obor OECD: Virology
http://www.ccsss.cz/index.php/ccsss/issue/view/37/67

Viral RNA (vRNA) of single-stranded positive-sense RNA viruses (+RNA viruses) resembles mRNA. It's 5' end bears a cap, a structure that is chemically composed of guanine nucleotide connected to the rest of the RNA via a 5′ to 5′ triphosphate linkage. The guanine base is methylated at the 7 position, in the Coronaviridae family this function is performed by the nsp14 methyltransferase (MTase)1. The vRNA is also modified at the 2′-hydroxy group on the first ribose sugar which is performed by another coronaviral enzyme, the nsp16 MTase1. We have characterized these enzymes in cells2 and solved crystal structures of both coronaviral enzymes (nsp14 and nsp16) in complex with their natural substrates (S-adenosyl methionine) and in complex with inhibitors3–5. The structural information is used to design a second generation of inhibitors with improved properties.
Trvalý link: https://hdl.handle.net/11104/0338570