Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00474778" target="_blank" >RIV/61388963:_____/17:00474778 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/srep41839" target="_blank" >https://www.nature.com/articles/srep41839</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/srep41839" target="_blank" >10.1038/srep41839</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor

Popis výsledku v původním jazyce

The alarmone nucleotide (p) ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence, making (p) ppGpp-mediated signaling a promising target for development of antibacterials. Although ppGpp itself is an activator of the ribosome-associated ppGpp synthetase RelA, several ppGpp mimics have been developed as RelA inhibitors. However promising, the currently available ppGpp mimics are relatively inefficient, with IC50 in the sub-mM range. In an attempt to identify a potent and specific inhibitor of RelA capable of abrogating (p) ppGpp production in live bacterial cells, we have tested a targeted nucleotide library using a biochemical test system comprised of purified Escherichia coli components. While none of the compounds fulfilled this aim, the screen has yielded several potentially useful molecular tools for biochemical and structural work.

Název v anglickém jazyce

Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor

Popis výsledku anglicky

The alarmone nucleotide (p) ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence, making (p) ppGpp-mediated signaling a promising target for development of antibacterials. Although ppGpp itself is an activator of the ribosome-associated ppGpp synthetase RelA, several ppGpp mimics have been developed as RelA inhibitors. However promising, the currently available ppGpp mimics are relatively inefficient, with IC50 in the sub-mM range. In an attempt to identify a potent and specific inhibitor of RelA capable of abrogating (p) ppGpp production in live bacterial cells, we have tested a targeted nucleotide library using a biochemical test system comprised of purified Escherichia coli components. While none of the compounds fulfilled this aim, the screen has yielded several potentially useful molecular tools for biochemical and structural work.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA15-11711S" target="_blank" >GA15-11711S: Vývoj molekulárních nástrojů pro ovlivňování a výzkum bakteriální stringentní odpovědi</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

Feb 3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

—

Kód UT WoS článku

000393552300001

EID výsledku v databázi Scopus

2-s2.0-85011591064