Nitric Oxide Inhibition of Glycyl Radical Enzymes and Their Activases.

ABSTRACT: Innate immune response cells produce high concentrations of the free radical nitric oxide (NO) in response to pathogen infection. The antimicrobial properties of NO include nonspecific damage to essential biomolecules and specific inactivation of enzymes central to aerobic metabolism. However, the molecular targets of NO in anaerobic metabolism are less understood. Here, we demonstrate that the Escherichia coli glycyl radical enzyme pyruvate formate lyase (PFL), which catalyzes the anaerobic metabolism of pyruvate, is irreversibly inhibited by NO. Using electron paramagnetic resonance and site-directed mutagenesis we show that NO destroys the glycyl radical of PFL. The activation of PFL by its cognate radical S-adenosyl-l-methionine-dependent activating enzyme (PFL-AE)

SUBMITTER: Caceres JC 

PROVIDER: S-EPMC11987019 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature