The Mismetallation of Enzymes During Oxidative Stress [Microbiology]

August 26th, 2014 by Imlay, J. A.

Mononuclear iron enzymes can tightly bind non-activating metals. How do cells avoid mismetallation? The model bacterium Escherichia coli may control its metal pools so that thermodynamics favor the correct metallation of each enzyme. This system is disrupted, however, by superoxide and hydrogen peroxide. These species oxidize ferrous iron and thereby displace it from many iron-dependent mononuclear enzymes. Ultimately zinc binds in its place, confers little activity, and imposes metabolic bottlenecks. Data suggests that Escherichia coli compensates by using thiols to extract the zinc and by importing manganese to replace the catalytic iron atom. Manganese resists oxidants and provides substantial activity.