6R3Y

M.tuberculosis nitrobindin with a cyanide molecule coordinated to the heme iron atom

Summary for 6R3Y

• Entry DOI: 10.2210/pdb6r3y/pdb
• Descriptor: UPF0678 fatty acid-binding protein-like protein ERS007657_00996, PROTOPORPHYRIN IX CONTAINING FE, CYANIDE ION, ... (4 entities in total)
• Functional Keywords: hemeproteins, beta-barrel, peroxynitrite detoxification, protein binding
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 19582.94

Authors

De Simone, G.,di Masi, A.,Polticelli, F.,Pesce, A.,Nardini, M.,Bolognesi, M.,Ciaccio, C.,Coletta, M.,Turilli, E.S.,Fasano, M.,Tognaccini, L.,Smulevich, G.,Abbruzzetti, S.,Viappiani, C.,Bruno, S.,Ascenzi, P. (deposition date: 2019-03-21, release date: 2020-04-08, Last modification date: 2024-11-06)

Primary citation

De Simone, G.,di Masi, A.,Vita, G.M.,Polticelli, F.,Pesce, A.,Nardini, M.,Bolognesi, M.,Ciaccio, C.,Coletta, M.,Turilli, E.S.,Fasano, M.,Tognaccini, L.,Smulevich, G.,Abbruzzetti, S.,Viappiani, C.,Bruno, S.,Ascenzi, P.
Mycobacterial and Human Nitrobindins: Structure and Function.
Antioxid.Redox Signal., 33:229-246, 2020

PubMed Abstract: 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 ferric Nb (-Nb(III)) and ferric Nb (-Nb(III)) have been investigated and compared with those of ferric Nb (-Nb(III), nitrophorins (-NP(III)s), and mammalian myoglobins. Data here reported demonstrate that -Nb(III), -Nb(III), and -Nb(III) share with -NP(III)s the capability to bind selectively nitric oxide, but display a very low reactivity, if any, toward histamine. Data obtained overexpressing -Nb in human embryonic kidney 293 cells indicate that -Nb localizes mainly in the cytoplasm and partially in the nucleus, thanks to a nuclear localization sequence encompassing residues Glu124-Leu154. Human -Nb corresponds to the -terminal domain of the human nuclear protein THAP4 suggesting that Nb may act as a sensor possibly modulating the THAP4 transcriptional activity residing in the -terminal region. Finally, we provide strong evidence that both -Nb(III) and -Nb(III) are able to scavenge peroxynitrite and to protect free l-tyrosine against peroxynitrite-mediated nitration. Data here reported suggest an evolutionarily conserved function of Nbs related to their role as nitric oxide sensors and components of antioxidant systems. Human THAP4 may act as a sensing protein that couples the heme-based Nb(III) reactivity with gene transcription. -Nb(III) seems to be part of the pool of proteins required to scavenge reactive nitrogen and oxygen species produced by the host during the immunity response.

PubMed: 32295384
DOI: 10.1089/ars.2019.7874

Experimental method

X-RAY DIFFRACTION (1.6 Å)