6r3w
M.tuberculosis nitrobindin with a water molecule coordinated to the heme iron atom
Structural highlights
FunctionNB1_MYCTU Heme-binding protein able to scavenge peroxynitrite and to protect free L-tyrosine against peroxynitrite-mediated nitration, by acting as a peroxynitrite isomerase that converts peroxynitrite to nitrate. Therefore, this protein likely plays a role in peroxynitrite sensing and in the detoxification of reactive nitrogen and oxygen species (RNS and ROS, respectively). In M.tuberculosis, could be part of the pool of proteins required to scavenge RNS and ROS produced by the host during the immunity response. Is able to bind nitric oxide (NO) in vitro, but may act as a sensor of peroxynitrite levels in vivo.[1] Publication Abstract from PubMedAIMS: Nitrobindins (Nbs) are evolutionary conserved all-beta-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. RESULTS: 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. INNOVATION: Data here reported suggest an evolutionarily conserved function of Nbs related to their role as gas sensors and components of the anti-oxidant system. CONCLUSION: 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. Mycobacterial and human nitrobindins: structure and function.,De Simone G, di Masi A, Vita GM, Polticelli F, Pesce A, Nardini M, Bolognesi M, Ciaccio C, Coletta M, Turilli ES, Fasano M, Tognaccini L, Smulevich G, Abbruzzetti S, Viappiani C, Bruno S, Ascenzi P Antioxid Redox Signal. 2020 Apr 16. doi: 10.1089/ars.2019.7874. PMID:32295384[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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