Luc Moens

• University of Antwerp

High energy consumption in the nervous system requires a continuous supply of O2. This role is assisted by proteins from the globin super-family in the nerve cells of invertebrates, where 'nerve hemoglobins' (nHbs) are mainly present at mM concentrations and exhibit oxygen affinities comparable to those of vertebrate myoglobins. To gain insight int...

Out of the 34 globins in Caenorhabditis elegans, GLB-33 is a putative globin-coupled transmembrane receptor with a yet unknown function. The globin domain (GD) contains a particularly hydrophobic haem pocket, that rapidly oxidizes to a low-spin hydroxide ligated haem state at physiological pH. Moreover, the GD has one of the fastest nitrite reducta...

The popular genetic model organism Caenorhabditis elegans (C. elegans) encodes 34 globins, whereby the few that are well-characterized show divergent properties besides the typical oxygen carrier function. Here, we present a biophysical characterization and expression analysis of C. elegans globin-3 (GLB-3). GLB-3 is predicted to exist in two isofo...

Globin-coupled sensors (GCS) usually consist of three domains: a sensor/globin, a linker, and a transmitter domain. The globin domain (GD), activated by ligand binding and/or redox change, induces an intramolecular signal transduction resulting in a response of the transmitter domain. Depending on the nature of the transmitter domain, GCSs can have...

Only recently it was discovered that haemoglobin (Hb) belongs to the standard gene repertoire of insects, although their tracheal system is used for respiration. A classical oxygen-carrying function of Hb is only obvious for hexapods living in hypoxic environments. In other insect species, including the common fruit fly Drosophila melanogaster, the...

Aims: Structural and functional characterization of the globin coupled sensors (GCS) of Azotobacter vinelandii (AvGReg) and Bordetella pertussis (BpeGReg). Results: UV/Vis and RR spectroscopies confirm the presence in Av GReg and Bpe GReg of a globin domain capable of reversible gaseous ligand binding. In Av GReg an influence of the transmitter...

In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by compar...

Supplementary Figures 1-8 and Supplementary Tables 1-2

Studies of CO ligand binding revealed that two protein states with different ligand affinities exist in the protoglobin from Methanosarcina acetivorans (in MaPgb*, residue Cys(E20)101 was mutated to Ser). The switch between the two states occurs upon the ligation of MaPgb*. In this work, site-directed mutagenesis was used to explore the role of sel...

We report the structural and biochemical characterization of GLB-33, a putative neuropeptide receptor that is exclusively expressed in the nervous system of the nematode Caenorhabditis elegans. This unique chimeric protein is composed of a 7 transmembrane domain, GLB-33 7TM, typical of a G-protein-coupled receptor, and of a globin domain, GLB-33 GD...

We report the structural and biochemical characterization of GLB-33, a putative neuropeptide receptor that is exclusively expressed in the nervous system of the nematode Caenorhabditis elegans. This unique chimeric protein is composed of a 7-transmembrane domain (7TM), GLB-33 7TM, typical of a G-protein-coupled receptor, and of a globin domain (GD)...

Electron paramagnetic resonance (EPR) data reveal large differences between the ferric ((13)C-)cyanide complexes of wild-type human neuroglobin (NGB) and its H64Q and F28L point mutants and the cyanide complexes of mammalian myo- and haemoglobin. The point mutations, which involve residues comprising the distal haem pocket in NGB, induce smaller, b...

The haem-based sensors are chimeric multi-domain proteins responsible for the cellular adaptive responses to environmental changes. The signal transduction is mediated by the sensing capability of the haem-binding domain, which transmits a usable signal to the cognate transmitter domain, responsible for providing the adequate answer. Four major fam...

Protoglobin from Methanosarcina acetivorans C2A (MaPgb), a strictly anaerobic methanogenic Archaea, is a dimeric haem-protein whose biological role is still unknown. As other globins, protoglobin can bind O2, CO and NO reversibly in vitro, but it displays specific functional and structural properties within members of the hemoglobin superfamily. CO...

Electron density at the haem distal site of MaPgb*. Stick representation of the distal site of (A) MaPgb*(III)-cyanide (yellow), (B) MaPgb*(III)-azide (green), (C) MaPgb*(III)-imidazole (orange), and (D) MaPgb*(III)-nicotinamide (brown). The electron density (2FO-FC map contoured at 1σ: cyan mesh) is shown around Trp(60)B9 and Tyr(61)B10, the haem,...

Data collection and refinement statistics for various derivative of ferric Ma Pgb*. (DOC)

Data collection and refinement statistics for cyanide derivative of ferric Ma Pgb* mutants. (DOC)

Xenon-binding site in MaPgb*(III)-azide and -cyanide complexes. Superimposition of MaPgb*(III)-cyanide (pink) onto the MaPgb*(III)-azide structure (green). The bound-Xe atom is shown as a sphere in black (MaPgb*(III)-azide) and in grey (MaPgb*(III)-cyanide). Residues lining the haem distal pocket and the Xenon-binding cavity are indicated and shown...

Functional and structural properties of protoglobin from Methanosarcina acetivorans, whose Cys(E20)101 residue was mutated to Ser (MaPgb*), and of mutants missing either the first 20N-terminal amino acids (MaPgb*-ΔN20 mutant), or the first 33N-terminal amino acids [N-terminal loop of 20 amino acids and a 13-residue Z-helix, preceding the globin fol...

Cytoglobin (Cygb) was recently discovered in the human genome and localized in different tissues. It was suggested to play tissue-specific protective roles, spanning from scavenging of reactive oxygen species in neurons to supplying oxygen to enzymes in fibroblasts. To shed light on the functioning of such versatile machinery, we have studied the p...

Experimental methods. Encapsulation of Cygb and He7Q Cygb*, Kinetic analysis, Crystallization and structural analysis of HE7Q Cygb*, and MD simulations. (DOC)

Superimposition of the first (cyan) and last (yellow) frames of the first eigenvector. a. Cygbh; b. Cygbp from HE7Q mutant; c. Cygbp from X-ray 3AG0; d. O2Cygb from HE7Q mutant; e. O2Cygb from X-ray 3AG0. (TIF)

Representation of the two conformations found for the indole ring of Trp151 in different X-ray structures. The endogenous bis-histidyl hexacoordinated protein (1UT0) is represented in blue and the CO-bound protein (3AG0) in gray. (TIF)

Close-up of the HE7Q Cygb* distal site. Comparisons of the CD loop and the E-helix as observed in the crystal structures of the HE7Q Cygb*-cyanide complex (gray ribbon) and (left) the Cygb* in the endogenous bis-histidyl hexacoordinated state (1UT0 subunit A, orange ribbon) or (right) Cygb* in the pentacoordinated state (1UT0 subunit B, magenta rib...

Time evolution of RMSD. Representation of the time evolution of the RMSD (Å) determined for the backbone (black) and heavy (red) atoms with regard to the corresponding energy minimized structures of the template models used to build up the simulated systems. (TIF)

Closeup of internal cavities. Closeup view of the internal cavities network identified in the crystal structure of chain A (a) and chain B (b) of the hexacoordinated form of human cytoglobin treated under Xe gas pressure (1UX9). Xe atoms are represented by cyan spheres, while the red contours correspond to energetically and sterically favourable Xe...

Representation of the average cavities found by ILS calculations. a. hCygb; b. pCygb from HE7Q mutant; c. pCygb from X-ray 3AG0; d. O2Cygb from HE7Q mutant; e. O2Cygb from X-ray 3AG0. (TIF)

Representative CO rebinding to COCygb solutions. Upper panel. CO rebinding kinetics to Cygb solutions equilibrated at 1 atm CO (blue circles 20°C; black circles 40°C) and 0.1 atm CO (cyan circles 20°C; red circles 40°C). Lower panel. Lifetime distributions associated with the rebinding kinetics in the top panel. CO rebinding kinetics shows a remark...

Representative analysis of CO rebinding to Cygb+CO gels. Global analysis of the CO rebinding kinetics to Cygb+CO gels (T = 40°C) equilibrated with 1 atm CO (black circles) and 0.1 atm CO (red circles). The fits (purple lines) are superimposed to the experimental data (circles). In the figures we have also reported the time course of the other relev...

Representative analysis of CO rebinding to HE7Q Cygb* solutions. Global analysis of the CO rebinding kinetics to HE7Q Cygb* solutions at T = 10°C (left) and T = 40°C (right), equilibrated with 1 atm CO (black circles) and 0.1 atm CO (red circles). The fits (purple lines) are superimposed to the experimental data (circles). In the figures we have al...

Comparison between microscopic rate constants for wt Cygb solutions, COCygb gels and Cygb+CO gels from the fit of the flash photolysis data, at 20°C. Activation enthalpies and entropies were estimated from the linear Eyring plots for each rate constant ki in the temperature range 10–40°C. (DOCX)

Activation free energies at 20°C for Cygb solutions and gels. (DOCX)

Representative analysis of CO rebinding to COCygb gels. Global analysis of the CO rebinding kinetics to COCygb gels (left 40°C, right 30°C) equilibrated with 1 atm CO (black circles) and 0.1 atm CO (red circles). The fits (purple lines) are superimposed to the experimental data (circles). In the figures we have also reported the time course of the...

Microscopic rate constants for HE7Q Cygb* solutions from the fit of the flash photolysis data, at 20°C. Activation enthalpies and entropies were estimated from the linear Eyring plots for each rate constant ki in the temperature range 10–40°C. (DOCX)

Data collection and refinement statistics for HE7Q Cygb*. (DOCX)

Representative analysis of CO rebinding to COCygb solutions. Analysis of the CO rebinding kinetics to wt Cygb solutions equilibrated with 1 atm CO (black circles) and 0.1 atm CO (red circles). Left, T = 30°C. Right, T = 40°C. The fits (purple lines) are superimposed to the experimental data (circles). In the figures we have also reported the time c...

Microscopic rate constants for Cygb from the fit of the flash photolysis data, at 20°C. Activation enthalpies and entropies were estimated from the linear Eyring plots for each rate constant ki in the temperature range 10–40°C. (DOCX)

Contribution (%) of the first 10 eigenvectors derived from essential dynamics to the conformational flexibility of the protein backbone. (DOCX)

Globins occur in all kingdoms of life where they fulfill a wide variety of functions. In the past they used to be primarily characterized as oxygen transport/storage proteins, but since the discovery of new members of the globin family like neuroglobin and cytoglobin, more diverse and complex functions have been assigned to this heterogeneous famil...

The Antarctic icefish Chaenocephalus aceratus lacks the globins common to most vertebrates, hemoglobin and myoglobin, but has retained neuroglobin in the brain. This conserved globin has been cloned, over-expressed and purified. To highlight similarities and differences, the structural features of the neuroglobin of this colourless-blooded fish wer...

UV-visible and RR spectra of D. mawNgb*. UV-visible (left) and RR (right) spectra of Fe3+, Fe2+, oxy, and CO complex of D. mawNgb*, in 20 mM Tris-HCl pH 7.6. The asterisks in the spectrum of the CO adduct indicate impurities. Experimental conditions are identical to those of C. aceNgb* (see Figure 1). (DOC)

RR spectra in the low-frequency region of D. mawNgb*. RR spectra in the low- frequency region of Fe2+, and CO complex of D. mawNgb*, in 20 mM Tris-HCl pH 7.6. Experimental conditions are identical to those of C. aceNgb* (see Figure 1). (DOC)

Autoxidation of the oxygenated forms of C. aceNgb* (green circles), D. mawNgb*(red circles) and human Ngb (black circles). The reaction was monitored at 580 nm and the traces were normalised using a spectrum collected at 4°C immediately after exposure to oxygen and a spectrum obtained in the presence of sodium ferricyanide as references for the pur...

CO dissociation kinetics of human Ngb, C. aceNgb* and D. mawNgb*. The Fe2+ complexes with CO were reacted treated with excess NO. (DOC)

Energy profile of migration pathways connecting cavity B to the solvent (SV) in CO-coordinated (A) and six-coordinated (B) species. From left to right: energy barriers of a ligand exiting from B to the solvent through cavities D (top), E (upper middle), F (lower middle) and G (bottom). In black, C. aceNgb*; in red, D. mawNgb*; in green, human Ngb....

Comparison of topologically similar ligand migration pathways in different works. Correspondence between ligand migration pathways identified in this work and those in [56] and [58]. (DOC)

Cloning and sequencing of Ngb cDNA. To obtain notothenioid-specific primers for Ngb cDNA, a partial Ngb gene was PCR-amplified from genomic DNA of several Antarctic notothenioid species with a pair of primers designed to conserved regions in teleost Ngb sequences available in the database. Sequencing of the PCR product from each species confirmed t...

RR spectra in the high-frequency region of the Fe2+ form, its CO complex, and the photolysed-CO product of C. aceNgb*. Experimental conditions for the Fe2+ and CO-adduct (20 mM Tris-HCl pH 7.6) are as reported in Figure 1. Photolysed-CO: 25 mW laser power at the sample, average of 2 spectra with 240-sec integration time (high- and low-frequency reg...

Normal mode assignments of the RR band of C. aceNgb* and D. mawNgb*. Normal mode assignments of the RR band (in cm−1) observed in the high-wavenumber region of the Fe3+, Fe2+ forms together with the oxy and CO adducts of C. aceNgb* and D. mawNgb*. (DOC)

The nerve tissue mini-hemoglobin from Cerebratulus lacteus (CerHb) displays an essential globin fold hosting a protein matrix tunnel held to allow traffic of small ligands to and from the heme. CerHb heme pocket hosts the distal TyrB10/GlnE7 pair, normally linked to low rates of O(2) dissociation and ultra-high O(2) affinity. However, CerHb affinit...

Electron paramagnetic resonance experiments reveal a significant difference between the principal g values (and hence ligand-field parameters) of the ferric cyanide-ligated form of different variants of the protoglobin of Methanosarcina acetivorans (MaPgb) and of horse heart myoglobin (hhMb). The largest principal g value of the ferric cyanide-liga...

Although molecular dynamics simulations suggest multiple interior pathways for O2 entry into and exit from globins, most experiments indicate well defined single pathways. In 2001, we highlighted the effects of large-to-small amino acid replacements on rates for ligand entry and exit onto the three-dimensional structure of sperm whale myoglobin. Th...

Protoglobin from Methanosarcina acetivorans (MaPgb) is a dimeric globin with peculiar structural properties such as a completely buried haem and two orthogonal tunnels connecting the distal cavity to the solvent. CO binding to and dissociation from MaPgb occur through a biphasic kinetics. We show that the heterogenous kinetics arises from binding t...

Resonance Raman spectrum of MaPgb* in the CO-bound form. The excitation wavelength was 413.1 nm, laser power employed was 100 mW. Detail of the low-frequency (A) and high-frequency (B) region of the RR spectrum of CO-bound ferrous MaPgb* recorded at 100 mW laser power. The photolysis effect can be used to identify the Fe-His stretching mode. This l...

Reductive nitrosylation of the MaPgb*(III)-cyanide complex, at pH 9.2 and 20.0°C. (A) Time courses of MaPgb*(III)-cyanide reductive nitrosylation at 410 nm and 425 nm (diamonds and squares, respectively). The analysis of data obtained at 410 nm (diamonds) according to Eqn. (1) allowed the determination of koff = (5.9±0.2)×10−5 s−1. The analysis of...

All globins belong to one of three families: the F (flavohemoglobin) and S (sensor) families that exhibit the canonical 3/3 α-helical fold, and the T (truncated 3/3 fold) globins characterized by a shortened 2/2 α-helical fold. All eukaryote 3/3 hemoglobins are related to the bacterial single domain F globins. It is known that Fungi contain flavohe...

MAFFT alignments of fungal Sgbs. (TIF)

Bayesian phylogenetic tree of complete fungal FHbs. Bayesian tree of a MAFFT v.6.850 alignment of 62 complete (globin+reductase domains) fungal FHbs, including all the sequences in Fig. 3, except the Fungi incertae sedis and the two outgroup sequences. Support values at branches represent Bayesian posterior probabilities (>0.5). The sequences are i...

NJ phylogenetic tree of fungal and bacterial FHbs. NJ tree of a TCOFFEE v. 9.01 alignment of 37 representative fungal FHbs and 55 representative bacterial FHbs using two bacterial Pgbs as outgroup. Only bootstrap values >50% are shown. The sequences are identified by the first three letters of the binary species name, the number of residues, and th...

MAFFT alignments of fungal FHbs. (TIF)

NJ phylogenetic tree of bacterial GCSs and Sgbs. NJ tree of a MUSCLE v.6.850 alignment of 60 representative bacterial GCSs including 5 single domain sensor globins (light brown boxes). Only bootstrap values >50% are shown. The first three letters of each part of the binary is followed by number of residues and by a letter denoting the nonglobin dom...

NJ phylogenetic tree of fungal and bacterial Sgbs. NJ tree of a TCOFFEE v. 9.01 alignment of 51 fungal, 57 bacterial (including 16 Pgbs), one rotifer and one heterolobosan Sgbs, using two Adgbs [16] as outgroup. Only bootstrap values >50% are shown. The sequences are identified by the first three letters of the binary species name, the number of re...

MUMSA scores for the five multiple alignment algorithms used in this work. (DOCX)

Hits obtained via PSIBLAST 2nd iteration using Aspergillus clavatus (Ascomycota) FHb globin domain (XP_001274889.1), as query, and selecting the first 40 fungal FHbs for the 2nd iteration. (DOCX)

Hits obtained via PSIBLAST 2nd iteration using Ajellomyces dermatidis (Ascomycota; Pezizomycotina; Eurotiomycetes) Sgb, 214aa (33–214) (XP_002625170.1), as query. (DOCX)

NJ phylogenetic tree of fungal Sgbs. NJ tree of a TCOFFEE v. 9.01 alignment of 59 fungal, one rotifer and one heterolobosan Sgbs. Only bootstrap values >50% are shown. The sequences are identified by the first three letters of the binary species name, the number of residues, and the first three or four letters of the phylum, followed by the first t...

Bayesian phylogenetic tree of fungal Sgbs. Bayesian tree based on a TCOFFEE v. 9.01 alignment of 59 fungal, one rotifer and one heterolobosan Sgbs. Support values at branches represent Bayesian posterior probabilities (>0.5). The sequences are identified by the first three letters of the binary species name, the number of residues, and the full phy...

Bayesian phylogenetic tree of bacterial GCSs and Sgbs. Bayesian tree based on a MUSCLE v.6.850 alignment of 60 representative bacterial GCSs including 5 single domain sensor globins (light brown boxes). Support values at branches represent Bayesian posterior probabilities (>0.5). The first three letters of each part of the binary species name is fo...

NJ phylogenetic tree of fungal and bacterial T1 globins. NJ tree of a TCOFFEE v. 9.01 alignment of 2 fungal (red and black arrows), 70 bacterial (blue), 4 euryarchaeote (purple) and 10 chlorophyte (green) T1 globins, using 2 Physcomitrella nsHbs as outgroup. Only bootstrap values >50% are shown. The sequences are identified by the first three lette...

Identified and putative globins in fungal genomes. (DOCX)

Hits obtained via PSIBLAST 2nd iteration using Coprinopsis cinerea (Basidiomycota) Sgb, 235aa (26–194) (XP_001838134.1), as query. (DOCX)

Hits obtained via BLASTP using the T1 globin domain from the Allomyces macrogynus (Blastocladiomycota) 1129aa chimeric protein (AMAG_16521T0), as query. (DOCX)

Hits obtained via BLASTP using the Batrachochytrium dendrobatidis (Chytridiomycota) T1 globin (BDEG_06358), as query. (DOCX)

Objective: Chronic hypoxia exists in many diseases, including cancer. The subject of our study is analysis of molecular pathways affected in the chronically hypoxic mouse brain. Materials and Methods: Using the emPAI protocol, we performed a quantitative proteomic approach to characterize the global proteome in the mouse brain exposed to 7% 02 for...

Comparative genomic studies have led to the recent identification of several novel globin types in the Metazoa. They have revealed a surprising evolutionary diversity of functions beyond the familiar O2 supply roles of hemoglobin and myoglobin. Here we report the discovery of a hitherto unrecognized family of proteins with a unique modular architec...

The function of neuroglobin, a member of the vertebrate globin family, is still unknown. In human neuroglobin (NGB), the formation of a disulfide bridge between the CysCD7 and CysD5 is known to affect the heme environment and its ligand-binding kinetics. Here, we show by means of EPR that the PheB10 residue plays a key role in transmitting the stru...

CO dissociation from GLB-26. CO dissociation after dilution of the carboxylated protein into an oxygenated buffer (1 atm O2). The rate limiting step of this reaction is koff CO since the O2 binding occurs within a few µs and is immediately followed by the iron oxidation. The insert shows the variation of absorption during this reaction which corres...

Caenorhabditis elegans globin GLB-26 (expressed from gene T22C1.2) has been studied in comparison with human neuroglobin (Ngb) and cytoglobin (Cygb) for its electron transfer properties. GLB-26 exhibits no reversible binding for O2 and a relatively low CO affinity compared to myoglobin-like globins. These differences arise from its mechanism of gas...

Protoglobin from Methanosarcina acetivorans C2A (MaPgb), a strictly anaerobic methanogenic Archaea, displays peculiar structural and functional properties within members of the hemoglobin superfamily. In fact, MaPgb-specific loops and a N-terminal extension (20 amino acid residues) completely bury the heme within the protein matrix. Therefore, the...

Protoglobin from Methanosarcina acetivorans C2A (MaPgb), a strictly anaerobic methanogenic Archaea, displays peculiar structural and functional properties within members of the hemoglobin superfamily. In fact, MaPgb-specific loops and a N-terminal extension (20 amino acid residues) completely bury the heme within the protein matrix. Therefore, the...

Extensive in silico search of the genome of Caenorhabditis elegans revealed the presence of 33 genes coding for globins that are all transcribed. These globins are very diverse in gene and protein structure and are localized in a variety of cells, mostly neurons. The large number of C. elegans globin genes is assumed to be the result of multiple ev...

The large apolar tunnel traversing the mini-hemoglobin from Cerebratulus lacteus (CerHb) has been examined by x-ray crystallography, ligand binding kinetics, and molecular dynamic simulations. The addition of 10 atm of xenon causes loss of diffraction in wild-type (wt) CerHbO2 crystals, but Leu-86(G12)Ala CerHbO2, which has an increased tunnel volu...

To determine whether purified Ascaris suum haemoglobin (AsHb) is a suitable vaccine candidate for the control of Ascaris infections, pigs were vaccinated with AsHb in combination with QuilA adjuvant and challenged with A. suum eggs. The number of liver lesions and worms in the intestine was assessed on day 14, 28 and 56 post-infection (p.i.). No si...

The globin-coupled sensor (GCS) of Geobacter sulfurreducens is unique amongst GCSs in that its signalling domain is a transmembrane domain with yet unknown function. In the present work we use X-band continuous-wave and pulsed electron paramagnetic resonance (EPR) to investigate the ferric form of the globin domain of the G. sulfurreducens GCS (GsG...

The oligomeric state and kinetics of ligand binding were measured for wild-type cytoglobin. Cytoglobin has the classical globin fold, with an extension at each extremity of about 20 residues. The extended length of cytoglobin leads to an ambiguous interpretation of its oligomeric state. Although the hydrodynamic diameter corresponds to that of a di...

The oligomeric state and kinetics of ligand binding were measured for wild-type cytoglobin. Cytoglobin has the classical globin fold, with an extension at each extremity of about 20 residues. The extended length of cytoglobin leads to an ambiguous interpretation of its oligomeric state. Although the hydrodynamic diameter corresponds to that of a di...

Background The genome of the nematode Caenorhabditis elegans contains more than 30 putative globin genes that all are transcribed. Although their translated amino acid sequences fit the globin fold, a variety of amino-acid substitutions and extensions generate a wide structural diversity among the putative globins. No information is available on th...

Purification of Recombinant C. elegans globins. detailed protocol for the purification of all studied globins.

Characteristics of the C. elegans globins studied. A table with all characteristics of the globins studied and an allignement of all globin sequences of C.elegans.

Data collection and refinement statistics for GLB-1*. Contains the data collection and refinement statistics and the stereochemical analysis of GLB-1* crystal structure.

Globin expression levels under hypoxic conditions. Graph of globin expression levels under hypoxic conditions.

Plants express three phylogenetic classes of hemoglobins (Hb) based on sequence analyses. Class 1 and 2 Hbs are full-length globins with the classical eight helix Mb-like fold, whereas Class 3 plant Hbs resemble the truncated globins found in bacteria. With the exception of the specialized leghemoglobins, the physiological functions of these plant...

Neuroglobin (Ngb), a member of the globin superfamily, was found in the brain of vertebrates and is suggested to play a neuroprotective function under hypoxic conditions by scavenging nitrogen monoxide (NO) through a dioxygenase activity. In order for such a reaction to efficiently take place and to minimize the release of reactive intermediates in...

Acute and chronic hypoxic episodes of the brain have been generally recognized as a common denominator of several neuropathologies of which cerebral ischemic stroke represents one of the leading causes of mortality and morbidity. In an attempt to clarify the plethora of molecular events elicited by ischemic or hypoxic stress, several studies have r...

Neuroglobin (Ngb) is a recently discovered globin that is predominantly expressed in the brain, retina and other nerve tissues of human and other vertebrates. Ngb has been shown to act as a neuroprotective factor, promoting neuronal survival in conditions of hypoxic-ischemic insult, such as those occurring during stroke. In this work, the conformat...

Neuroglobin is a recently discovered member of the globin family, mainly observed in neurons and retina. Despite the low sequence identity (less than 20% over the whole sequence for the human proteins), the general fold of neuroglobin closely resembles that of myoglobin. The latter is a paradigmatic protein for folding studies, whereas much less is...