Biochemical characterization of recombinant influenza A polymerase heterotrimer complex: Polymerase activity and mechanisms of action of nucleotide analogs

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00481074" target="_blank" >RIV/61388963:_____/17:00481074 - isvavai.cz</a>

Result on the web

<a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185998" target="_blank" >http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185998</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0185998" target="_blank" >10.1371/journal.pone.0185998</a>

Result language

angličtina

Original language name

Biochemical characterization of recombinant influenza A polymerase heterotrimer complex: Polymerase activity and mechanisms of action of nucleotide analogs

Original language description

Influenza polymerase is a heterotrimer protein with both endonuclease and RNA-dependent RNA polymerase (RdRp) activity. It plays a critical role in viral RNA replication and transcription and has been targeted for antiviral drug development. In this study, we characterized the activity of recombinant RdRp purified at 1:1:1 ratio in both ApG-primed RNA replication and mRNA-initiated RNA transcription. The heterotrimer complex showed comparable activity profiles to that of viral particle derived crude replication complex, and in contrast to the crude replication complex, was suitable for detailed mechanistic studies of nucleotide incorporation. The recombinant RdRp was further used to examine distinct modes of inhibition observed with five different nucleotide analog inhibitors, and the apparent steady-state binding affinity K-app was measured for selected analogs to correlate antiviral activity and enzymatic inhibition with substrate efficiency.

Czech name

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Czech description

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Type

J_imp - 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

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

PLoS ONE

ISSN

1932-6203

e-ISSN

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Volume of the periodical

12

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

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UT code for WoS article

000412754400058

EID of the result in the Scopus database

2-s2.0-85031281165