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

ABSTRACT: Non-enzymatic oxidative processes in living organisms are one of the inevitable consequences of respiration and environmental conditions. They 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 functional consequences. Methionine oxidation can be reverted enzymatically by methionine sulfoxide reductases (Msrs). The two enzyme classes known to fulfil this role are MsrA (reducing (S)-sulfoxides), and MsrB (reducing (R)-sulfoxides). They are strictly stereoselective and conserved throughout the tree of life. Under stress conditions such as stationary phase and nutrient starvation, E.coli upregulates expression of MsrA but similar effect has not been described for MsrB, raising a conundrum of the pathway enabling 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, (R)-sulfoxide-reducing counterpart. 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.

INSTRUMENT(S): LTQ FT

ORGANISM(S): Escherichia Coli

SUBMITTER: Karel Harant  

LAB HEAD: Kvido Strisovsky

PROVIDER: PXD013610 | Pride | 2019-06-12

REPOSITORIES: Pride