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

Abstract

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 NO3− 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.