Molecular Mechanisms of the Methionine Sulfoxide Reductase System from Neisseria meningitidis

Abstract

Neisseria meningitidis, an obligate pathogenic bacterium in humans, has acquired different defense mechanisms to detect and fight the oxidative stress generated by the host’s defense during infection. A notable example of such a mechanism is the PilB reducing system, which repairs oxidatively-damaged methionine residues. This review will focus on the catalytic mechanism of the two methionine sulfoxide reductase (MSR) domains of PilB, which represent model enzymes for catalysis of the reduction of a sulfoxide function by thiols through sulfenic acid chemistry. The mechanism of recycling of these MSR domains by various “Trx-like” disulfide oxidoreductases will also be discussed.

Functional characterization of methionine sulfoxide reductases from Leptospira interrogans

“…These thiol-dependent redox proteins could be a source of reducing equivalents and catalyze the reduction of the intermediate disulfide in the case of LinMsrAs or the intermediate sulfenic acid in LinMsrB (see Fig. 14), thus regenerating the Msrs to their (reduced) thiol form in the periplasm of L. interrogans (as already described for other bacteria [9,81]). This hypothesis tempts us to propose new experiments that will be evaluated in future studies.…”

“…Streptococcus pneumoniae [78], Streptococcus gordonii [79], Staphylococcus aureus [80], and Neisseria meningitidis [81]. In view that the L. interrogans canonical Trx system (as well as a putative Grx and the GSH) exhibits a cytoplasmic location, a question to be asked is, what other system or redox protein could be a substrate for the Msrs in the periplasm?…”

Structure and Electron-Transfer Pathway of the Human Methionine Sulfoxide Reductase MsrB3

“…Other sources of reducing equivalents in the ER are also possible, including reduced glutathione (25). For comparison, recycling of MsrB enzymes in the bacterial periplasm, an environment analogous to the ER in its support of oxidative protein folding, involves electrons transferred across the cell membrane by the enzyme DsbD (7). It should be noted, however, that oxidized MsrB3 can convert free methionine to the sulfoxide (10), indicating that an environment that favors conversion of the MsrB3 active site to sulfenic acid will, in turn, drive formation of MetSO.…”

A Novel Small RNA, DsrO, in Deinococcus radiodurans Promotes Methionine Sulfoxide Reductase ( msrA ) Expression for Oxidative Stress Adaptation

“…Bacterial mutants for msrA and/or msrB display ROS-sensitive phenotypes. The two forms of Msr that reduce l -Met-S-(O) are MsrA and MsrB; MsrA functions on both peptide-bound l -Met-S-(O) and free l -Met-S-(O) ( 23 , 24 ). Msr proteins are evolutionarily conserved and function similarly in response to ROS exposure.…”