Evolution of YacG to safeguard DNA gyrase from external perturbation

Biswas, Prabir Kumar; Sengupta, Surajit; Nagaraja, Valakunja

doi:10.1016/j.resmic.2023.104093

Cited by 1 publication

(4 citation statements)

References 66 publications

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“…This upregulated YacG then binds to gyrase, forming a gyrase-YacG complex that is incapable of binding to DNA (Figure 6). As a result, this complex formation prevents the subsequent steps leading to DNA damage and cell death, thereby protecting the cells from the action of gyrase poisons [135]. This is consistent with limiting spurious ATP turnover outside of catalysis, which is a previously noted consequence of YacG-gyrase interactions [136].…”

Section: Yacgsupporting

confidence: 78%

“…This is consistent with limiting spurious ATP turnover outside of catalysis, which is a previously noted consequence of YacG-gyrase interactions [136]. Interestingly, the site of YacG binding has been independently identified as a novel site for inhibitor binding through compound Subsequent studies clarified a highly protective role for YacG, and its expression appears to be induced by stresses that impact DNA gyrase integrity, including multiple classes of antibiotics that are less effective when YacG is present [135]. In bacterial cells containing the yacG gene, the oxidative stress induced by gyrase poisoning triggers an increase in the expression of YacG.…”

Section: Yacgsupporting

confidence: 74%

“…YacG is a 65-amino acid protein encoded within the genome of many proteobacteria [135], including Escherichia coli, and it has been identified as an endogenous inhibitor of DNA gyrase. The overexpression of YacG hampered E. coli cell growth by the inhibition of gyrase supercoiling and relaxation activities [136].…”

Section: Yacgmentioning

confidence: 99%

“…Subsequent studies clarified a highly protective role for YacG, and its expression appears to be induced by stresses that impact DNA gyrase integrity, including multiple classes of antibiotics that are less effective when YacG is present [135]. In bacterial cells containing the yacG gene, the oxidative stress induced by gyrase poisoning triggers an increase in the expression of YacG.…”

Section: Yacgmentioning

confidence: 99%

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Friend or Foe: Protein Inhibitors of DNA Gyrase

Ruan,

Tu,

Bourne

2024

Biology

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DNA gyrase is essential for the successful replication of circular chromosomes, such as those found in most bacterial species, by relieving topological stressors associated with unwinding the double-stranded genetic material. This critical central role makes gyrase a valued target for antibacterial approaches, as exemplified by the highly successful fluoroquinolone class of antibiotics. It is reasonable that the activity of gyrase could be intrinsically regulated within cells, thereby helping to coordinate DNA replication with doubling times. Numerous proteins have been identified to exert inhibitory effects on DNA gyrase, although at lower doses, it can appear readily reversible and therefore may have regulatory value. Some of these, such as the small protein toxins found in plasmid-borne addiction modules, can promote cell death by inducing damage to DNA, resulting in an analogous outcome as quinolone antibiotics. Others, however, appear to transiently impact gyrase in a readily reversible and non-damaging mechanism, such as the plasmid-derived Qnr family of DNA-mimetic proteins. The current review examines the origins and known activities of protein inhibitors of gyrase and highlights opportunities to further exert control over bacterial growth by targeting this validated antibacterial target with novel molecular mechanisms. Furthermore, we are gaining new insights into fundamental regulatory strategies of gyrase that may prove important for understanding diverse growth strategies among different bacteria.

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Section: Yacgsupporting

confidence: 78%

Section: Yacgsupporting

confidence: 74%