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.
Highlights
Neisseria meningitidis is the infectious agent responsible for meningitis and septicemia.Its pathogenicity depends on its ability to resist activated oxygen and nitrate species produced by host macrophages in response to infection
In order for the catalytic activity to be regenerated, methionine sulfoxide reductase (MSR) need to be reduced at the end of the catalytic cycle, a function performed by Trx in the cytoplasm and the N-terminal domain (N-ter) domain in the periplasm
In PilB, the N-ter domain efficiently reduces only the MSRB domain via an intramolecular In PilB, the N-ter domain efficiently reduces only the MSRB domain via an intramolecular mechanism, whereas the reduction of the MSRA domain depends on the classical Trx-like mechanism, whereas the reduction of the MSRA domain depends on the classical Trx-like intermolecular mechanism (Figure 5)
Summary
Neisseria meningitidis is the infectious agent responsible for meningitis and septicemia. Analysis by protein sequence identity of publicly-available translated genome data, shows that the PilB protein is encoded by only a few bacterial genomes These include human commensal and pathogenic bacteria such as Neisseriae (N. meningitidis, N. gonorrhoeae, N. lactamica and N. cinerea), as well as the bacteria present in dental plaque, such as Fusobacterium nucleatum and Kingella oralis, and the non-pathogenic extremophile bacterium Psychrobacter cryohalolentis (Figure 1). Expression studies in Escherichia coli, the truncated form of N. meningitidis PilB has been shown to be produced by an internal reinitiation mechanism during translation, at an AUG codon corresponding to the Met195 residue of the whole protein [5]. The linker regions between N-ter and MSRA, and MSRA and MsrB are located between residues 176 and 195, and 357 and 382, respectively.
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