Mycobacterial and human nitrobindins: structure and function.

Nitrobindins (Nbs) are evolutionary conserved all-β-barrel heme-proteins displaying a highly solvent-exposed heme-Fe(III) atom. The physiological role(s) of Nbs is almost unknown. Here, the structural and functional properties of the Mycobacterium tuberculosis Nb (Mt-Nb(III)) and Homo sapiens Nb (Hs-Nb(III)) have been investigated and compared with those of Arabidopsis thaliana Nb (At-Nb(III), of the hematophagous bug Rodius prolixus nitrophorins (Rp-NP(III)s), and of mammalian myoglobins.Data here reported demonstrate that Mt-Nb(III), At-Nb(III), and Hs-Nb(III) share with Rp-NP(III)s the capability to bind selectively NO, but display a very low reactivity, if any, towards histamine. Data obtained overexpressing Hs-Nb in HEK293 cells indicate that Hs-Nb localizes mainly in the cytoplasm and partially in the nucleus thanks to a nuclear localization sequence encompassing residues Glu124-Leu154. Human Hs-Nb corresponds to the C-terminal domain of the human nuclear protein THAP4, and our data suggest that Nb may act as a sensor possibly modulating the THAP4 transcriptional activity residing in the N-terminal region. Finally, we provide strong evidence that both Mt-Nb(III) and Hs-Nb(III) are able to scavenge peroxynitrite and to protect dose-dependently free L-tyrosine against peroxynitrite-mediated nitration.Data here reported suggest an evolutionarily conserved function of Nbs related to their role as gas sensors and components of the anti-oxidant system.Human THAP4 may act as a sensing protein that couples the heme-based Nb(III) reactivity with gene transcription. Besides, Mt-Nb(III) seems to be part of the pool of proteins required to scavenge RNS and ROS produced by the host during the immunity response.