Structural and functional studies of coronaviral RNA-methyltransferases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00567310" target="_blank" >RIV/61388963:_____/22:00567310 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.ccsss.cz/index.php/ccsss/issue/view/37/67" target="_blank" >http://www.ccsss.cz/index.php/ccsss/issue/view/37/67</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Structural and functional studies of coronaviral RNA-methyltransferases

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Structural and functional studies of coronaviral RNA-methyltransferases

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů