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

0510367 - ÚOCHB 2020 RIV GB eng J - Článek v odborném periodiku
Makukhin, N. - Havelka, V. - Poláchová, Edita - Rampírová, Petra - Tarallo, V. - Stříšovský, Kvido - Míšek, J.
Resolving oxidative damage to methionine by an unexpected membrane-associated stereoselective reductase discovered using chiral fluorescent probes.
FEBS Journal. Roč. 286, č. 20 (2019), s. 4024-4035. ISSN 1742-464X. E-ISSN 1742-4658
Grant CEP: GA ČR(CZ) GA18-09556S; GA MŠMT(CZ) EF16_019/0000729; GA MŠMT LO1302
Institucionální podpora: RVO:61388963
Klíčová slova: chirality * fluorescent probes * methionine oxidation * oxidoreductases * redox biology
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.392, rok: 2019
Způsob publikování: Omezený přístup
https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.14951

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.
Trvalý link: http://hdl.handle.net/11104/0300882