Human nitrobindin: the first example of an all-β-barrel ferric heme-protein that catalyzes peroxynitrite detoxification

Nitrobindins (Nbs), constituting a heme-protein family spanning from bacteria to Homo sapiens, display an all-β-barrel structural organization. Human Nb has been described as a domain of the nuclear protein named THAP4, whose physiological function is still unknown. We report the first evidence of the heme-Fe(III)-based detoxification of peroxynitrite by the all-β-barrel C-terminal Nb-like domain of THAP4. Ferric human Nb (Nb(III)) catalyzes the conversion of peroxynitrite to ${\text{NO}}_3^{-}$ and impairs the nitration of free l-tyrosine. The rate of human Nb(III)-mediated scavenging of peroxynitrite is similar to those of all-α-helical horse heart and sperm whale myoglobin and human hemoglobin, generally taken as the prototypes of all-α-helical heme-proteins. The heme-Fe(III) reactivity of all-β-barrel human Nb(III) and all-α-helical prototypical heme-proteins possibly reflects the out-to-in-plane transition of the heme-Fe(III)-atom preceding peroxynitrite binding. Human Nb(III) not only catalyzes the detoxification of peroxynitrite but also binds NO, possibly representing a target of reactive nitrogen species.

human nitrobindin; kinetics; peroxynitrite scavenging; protection of l‐tyrosine nitration.