Resolving oxidative damage to methionine by an unexpected membrane-associated stereoselective reductase discovered using chiral fluorescent probes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00510367" target="_blank" >RIV/61388963:_____/19:00510367 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/19:10401434 RIV/00216208:11110/19:10401434

Výsledek na webu

<a href="https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.14951" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.14951</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.14951" target="_blank" >10.1111/febs.14951</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Resolving oxidative damage to methionine by an unexpected membrane-associated stereoselective reductase discovered using chiral fluorescent probes

Popis výsledku v původním jazyce

Nonenzymatic oxidative processes in living organisms are among the inevitable consequences of respiration and environmental conditions. These oxidative processes can lead to the formation of two stereoisomers (R and S) of methionine sulfoxide, and the redox balance between methionine and methionine sulfoxide in proteins has profound implications on their function. Methionine oxidation can be reverted enzymatically by methionine sulfoxide reductases (Msrs). The two enzyme classes known to fulfill this role are MsrA, reducing the (S)-isomer, and MsrB, reducing the (R)-isomer of methionine sulfoxide. They are strictly stereoselective and conserved throughout the tree of life. Under stress conditions such as stationary phase and nutrient starvation, Escherichia coli upregulates the expression of MsrA but a similar effect has not been described for MsrB, raising the conundrum of which pathway enables reduction of the (R)-isomer of methionine sulfoxide in these conditions. Using the recently developed chiral fluorescent probes Sulfox-1, we show that in stationary phase-stressed E. coli, MsrA does have a stereocomplementary activity reducing the (R)-isomer of methionine sulfoxide. However, this activity is not provided by MsrB as expected, but instead by the DMSO reductase complex DmsABC, widely conserved in bacteria. This finding reveals an unexpected diversity in the metabolic enzymes of redox regulation concerning methionine, which should be taken into account in any antibacterial strategies exploiting oxidative stress.

Název v anglickém jazyce

Resolving oxidative damage to methionine by an unexpected membrane-associated stereoselective reductase discovered using chiral fluorescent probes

Popis výsledku anglicky

Nonenzymatic oxidative processes in living organisms are among the inevitable consequences of respiration and environmental conditions. These oxidative processes can lead to the formation of two stereoisomers (R and S) of methionine sulfoxide, and the redox balance between methionine and methionine sulfoxide in proteins has profound implications on their function. Methionine oxidation can be reverted enzymatically by methionine sulfoxide reductases (Msrs). The two enzyme classes known to fulfill this role are MsrA, reducing the (S)-isomer, and MsrB, reducing the (R)-isomer of methionine sulfoxide. They are strictly stereoselective and conserved throughout the tree of life. Under stress conditions such as stationary phase and nutrient starvation, Escherichia coli upregulates the expression of MsrA but a similar effect has not been described for MsrB, raising the conundrum of which pathway enables reduction of the (R)-isomer of methionine sulfoxide in these conditions. Using the recently developed chiral fluorescent probes Sulfox-1, we show that in stationary phase-stressed E. coli, MsrA does have a stereocomplementary activity reducing the (R)-isomer of methionine sulfoxide. However, this activity is not provided by MsrB as expected, but instead by the DMSO reductase complex DmsABC, widely conserved in bacteria. This finding reveals an unexpected diversity in the metabolic enzymes of redox regulation concerning methionine, which should be taken into account in any antibacterial strategies exploiting oxidative stress.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

FEBS Journal

ISSN

1742-464X

e-ISSN

—

Svazek periodika

286

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

4024-4035

Kód UT WoS článku

000491083000007

EID výsledku v databázi Scopus

2-s2.0-85067400046