Human nitrobindin: the first example of an all-?-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-?-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-?-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-?-helical horse heart and sperm whale myoglobin and human hemoglobin, generally taken as the prototypes of all-?-helical heme-proteins. The heme-Fe(III) reactivity of all-?-barrel human Nb(III) and all-?-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.

SUBMITTER: De Simone G 

PROVIDER: S-EPMC6275384 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature