Nitrophorins and nitrobindins: structure and function

Abstract

Classical all α-helical globins are present in all living organisms and are ordered in three lineages: (i) flavohemoglobins and single domain globins, (ii) protoglobins and globin coupled sensors and (iii) truncated hemoglobins, displaying the 3/3 or the 2/2 all α-helical fold. However, over the last two decades, all β-barrel and mixed α-helical-β-barrel heme-proteins displaying hemebased functional properties (e.g. ligand binding, transport and sensing) closely similar to those of all α-helical globins have been reported. Monomeric nitrophorins (NPs) and α 1 -microglobulin (α 1 -m), belonging to the lipocalin superfamily and nitrobindins (Nbs) represent prototypical heme-proteins displaying the all β-barrel and mixed α-helical-β-barrel folds. NPs are confined to the Reduviidae and Cimicidae families of Heteroptera, whereas α 1 -m and Nbs constitute heme-protein families spanning bacteria to Homo sapiens. The structural organization and the reactivity of the stable ferric solvent-exposed heme-Fe atom suggest that NPs and Nbs are devoted to NO transport, storage and sensing, whereas Hs-α 1 -m participates in heme metabolism. Here, the structural and functional properties of NPs and Nbs are reviewed in parallel with those of sperm whale myoglobin, which is generally taken as the prototype of monomeric globins.

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

“…Furthermore, the mixed a-helical-b-barrel heme-proteins human a1-microglobulin and Cimex lectularius NP have been described [21,[25][26][27]. Nbs display a ten-stranded antiparallel b-barrel fold in which the penta-coordinated heme-Fe atom is secured to the protein by the proximal His residue [21][22][23][24]27]. In Nbs, the heme is highly solvent exposed and is stable in the ferric form, allowing to bind NO [21][22][23][24].…”

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

“…Small β-barrels such as lipocalins (i.e., transporters of small hydrophobic molecules that play vital roles in many biological processes [ 35 ]) or heme-containing nitrophorins/nitrobindins of the all-β-barrel type (involved in NO transport, storage and sensing as well as heme metabolism [ 36 ]) usually constitute eight to ten antiparallel β-strands and tightly packed hydrophobic or hydrophilic barrel interiors [ 37 ]. Membrane-bound β-barrels are confined to mitochondrial and chloroplast membranes and the outer membranes of Gram-negative bacteria [ 38 ].…”

Structural and (Pseudo-)Enzymatic Properties of Neuroglobin: Its Possible Role in Neuroprotection

“…The most striking differences between the 2/2 and the 3/3 globin folds are: ( i ) the drastically shortened or absent A-helix, ( ii ) the alteration of the C-E region, and ( iii ) the presence of a long polypeptide segment, which precedes the short α-helix F where the proximal HisF8 residue is located coordinating the heme-Fe atom [ 2 , 4 , 7 , 8 , 21 ]. Over the last two decades, all β-barrel non-canonical globins (i.e., nitrophorins and nitrobindins) mainly devoted to NO metabolism have been reported [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Of note, human nitrobindin, corresponding to the C -terminal domain of the nuclear protein THAP4, has been hypothesized to act as a NO sensor modulating the transcriptional activity residing at the N -terminus [ 25 , 26 , 27 , 28 , 29 ].…”

“…Over the last two decades, all β-barrel non-canonical globins (i.e., nitrophorins and nitrobindins) mainly devoted to NO metabolism have been reported [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Of note, human nitrobindin, corresponding to the C -terminal domain of the nuclear protein THAP4, has been hypothesized to act as a NO sensor modulating the transcriptional activity residing at the N -terminus [ 25 , 26 , 27 , 28 , 29 ].…”