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Frontiers in Molecular Biosciences 2022Hemerythrin is an oxygen-binding protein originally found in certain marine invertebrates. Oxygen reversibly binds at its non-heme diiron center, which consists of two... (Review)
Review
Hemerythrin is an oxygen-binding protein originally found in certain marine invertebrates. Oxygen reversibly binds at its non-heme diiron center, which consists of two oxo-bridged iron atoms bound to a characteristic conserved set of five His residues, one Glu residue, and one Asp residue. It was recently discovered that several bacteria utilize hemerythrin as an oxygen- and redox-sensing domain in responding to changes in cellular oxygen concentration or redox status, and immediately adapt to these environmental changes in order to maintain important physiological processes, including chemotaxis and c-di-GMP synthesis and degradation. This Mini Review focuses on the recent progress made on structural and functional aspects of these emerging bacterial hemerythrin domain-containing oxygen and redox sensors, revealing characteristic features of this family of proteins.
PubMed: 35992274
DOI: 10.3389/fmolb.2022.967059 -
Frontiers in Plant Science 2019Iron (Fe) is an essential nutrient for plants, but at the same time its redox properties can make it a dangerous toxin inside living cells. Homeostasis between uptake,... (Review)
Review
Iron (Fe) is an essential nutrient for plants, but at the same time its redox properties can make it a dangerous toxin inside living cells. Homeostasis between uptake, use and storage of Fe must be maintained at all times. A small family of unique hemerythrin E3 ubiquitin ligases found in green algae and plants play an important role in avoiding toxic Fe overload, acting as negative regulators of Fe homeostasis. Protein interaction data showed that they target specific transcription factors for degradation by the 26S proteasome. It is thought that the activity of the E3 ubiquitin ligases is controlled by Fe binding to the N-terminal hemerythrin motifs. Here, we discuss what we have learned so far from studies on the HRZ (Hemerythrin RING Zinc finger) proteins in rice, the homologous BTS (BRUTUS) and root-specific BTSL (BRUTUS-LIKE) in Arabidopsis. A mechanistic model is proposed to help focus future research questions towards a full understanding of the regulatory role of these proteins in Fe homeostasis in plants.
PubMed: 30815004
DOI: 10.3389/fpls.2019.00098 -
Molecules (Basel, Switzerland) Jun 2022Repair of Iron Center proteins (RIC) form a family of di-iron proteins that are widely spread in the microbial world. RICs contain a binuclear nonheme iron site in a... (Review)
Review
Repair of Iron Center proteins (RIC) form a family of di-iron proteins that are widely spread in the microbial world. RICs contain a binuclear nonheme iron site in a four-helix bundle fold, two basic features of hemerythrin-like proteins. In this work, we review the data on microbial RICs including how their genes are regulated and contribute to the survival of pathogenic bacteria. We gathered the currently available biochemical, spectroscopic and structural data on RICs with a particular focus on RIC (also known as YtfE), which remains the best-studied protein with extensive biochemical characterization. Additionally, we present novel structural data for YtfE harboring a di-manganese site and the protein's affinity for this metal. The networking of protein interactions involving YtfE is also described and integrated into the proposed physiological role as an iron donor for reassembling of stress-damaged iron-sulfur centers.
Topics: Bacterial Proteins; Escherichia coli; Escherichia coli Proteins; Hemerythrin; Iron; Iron-Sulfur Proteins; Sulfur
PubMed: 35807291
DOI: 10.3390/molecules27134051 -
Cellular and Molecular Life Sciences :... Jan 2017It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A... (Review)
Review
It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. The purpose of this review is to evaluate the true extent of oxygen-transport protein dynamics in innate immunity, and to impress upon the reader the multi-functionality of these ancient proteins on the basis of their structures. In this context, erythrocyte-pathogen antibiosis and the immune competences of various erythroid cells are compared across diverse taxa.
Topics: Animals; Biological Transport; Hemerythrin; Hemocyanins; Hemoglobins; Humans; Immunity, Innate; Oxygen
PubMed: 27518203
DOI: 10.1007/s00018-016-2326-7 -
Tanpakushitsu Kakusan Koso. Protein,... May 1987
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The Journal of Biological Chemistry Mar 2022The hemerythrin-like protein from Mycobacterium kansasii (Mka HLP) is a member of a distinct class of oxo-bridged diiron proteins that are found only in mycobacterial...
The hemerythrin-like protein from Mycobacterium kansasii (Mka HLP) is a member of a distinct class of oxo-bridged diiron proteins that are found only in mycobacterial species that cause respiratory disorders in humans. Because it had been shown to exhibit weak catalase activity and a change in absorbance on exposure to nitric oxide (NO), the reactivity of Mka HLP toward NO was examined under a variety of conditions. Under anaerobic conditions, we found that NO was converted to nitrite (NO) via an intermediate, which absorbed light at 520 nm. Under aerobic conditions NO was converted to nitrate (NO). In each of these two cases, the maximum amount of nitrite or nitrate formed was at best stoichiometric with the concentration of Mka HLP. When incubated with NO and HO, we observed NO peroxidase activity yielding nitrite and water as reaction products. Steady-state kinetic analysis of NO consumption during this reaction yielded a K for NO of 0.44 μM and a k/K of 2.3 × 10 Ms. This high affinity for NO is consistent with a physiological role for Mka HLP in deterring nitrosative stress. This is the first example of a peroxidase that uses an oxo-bridged diiron center and a rare example of a peroxidase utilizing NO as an electron donor and cosubstrate. This activity provides a mechanism by which the infectious Mycobacterium may combat against the cocktail of NO and superoxide (O) generated by macrophages to defend against bacteria, as well as to produce NO to adapt to hypoxic conditions.
Topics: Hemerythrin; Hydrogen Peroxide; Kinetics; Mycobacterium kansasii; Nitrates; Nitric Oxide; Nitrites; Nitrogen Dioxide; Oxidoreductases; Peroxidases
PubMed: 35150744
DOI: 10.1016/j.jbc.2022.101696 -
FEMS Microbiology Letters Feb 2008Hemerythrins are oxygen-binding proteins found in the body fluids and tissues of certain invertebrates. Oxygen is bound at a nonheme iron centre consisting of two... (Review)
Review
Hemerythrins are oxygen-binding proteins found in the body fluids and tissues of certain invertebrates. Oxygen is bound at a nonheme iron centre consisting of two oxo-bridged iron atoms bound to a characteristic set of conserved histidine: aspartate and glutamate residues with the motifs H-HxxxE-HxxxH-HxxxxD. It has recently been demonstrated biochemically that two bacterial proteins bearing the same motifs do in fact possess similar iron centres and bind oxygen in the same way. The recent profusion of prokaryotic genomic sequence data has shown that proteins bearing hemerythrin motifs are present in a wide variety of bacteria, and a few archaea. Some of these are short proteins as in eukaryotes; others appear to consist of a hemerythrin domain fused to another domain, generally a putative signal transduction domain such as a methyl-accepting chemotaxis protein, a histidine kinase, or a GGDEF protein (cyclic di-GMP synthase). If, as initial evidence suggests, these are in fact hemerythrin-like oxygen-binding proteins, then their diversity in prokaryotes far exceeds that seen in eukaryotes. Here, a survey is presented of prokaryotic protein sequences bearing hemerythrin-like motifs, for which the designation 'bacteriohemerythrins' is proposed, and their functions are speculated.
Topics: Archaea; Archaeal Proteins; Bacteria; Bacterial Proteins; Hemerythrin; Phylogeny; Protein Structure, Tertiary
PubMed: 18081840
DOI: 10.1111/j.1574-6968.2007.01011.x -
Protein Science : a Publication of the... Apr 2018Hemerythrin-like proteins have generally been studied for their ability to reversibly bind oxygen through their binuclear nonheme iron centers. However, in recent years,...
Hemerythrin-like proteins have generally been studied for their ability to reversibly bind oxygen through their binuclear nonheme iron centers. However, in recent years, it has become increasingly evident that some members of the hemerythrin-like superfamily also participate in many other biological processes. For instance, the binuclear nonheme iron site of YtfE, a hemerythrin-like protein involved in the repair of iron centers in Escherichia coli, catalyzes the reduction of nitric oxide to nitrous oxide, and the human F-box/LRR-repeat protein 5, which contains a hemerythrin-like domain, is involved in intracellular iron homeostasis. Furthermore, structural data on hemerythrin-like domains from two proteins of unknown function, PF0695 from Pyrococcus furiosus and NMB1532 from Neisseria meningitidis, show that the cation-binding sites, typical of hemerythrin, can be absent or be occupied by metal ions other than iron. To systematically investigate this functional and structural diversity of the hemerythrin-like superfamily, we have collected hemerythrin-like sequences from a database comprising fully sequenced proteomes and generated a cluster map based on their all-against-all pairwise sequence similarity. Our results show that the hemerythrin-like superfamily comprises a large number of protein families which can be classified into three broad groups on the basis of their cation-coordinating residues: (a) signal-transduction and oxygen-carrier hemerythrins (H-HxxxE-HxxxH-HxxxxD); (b) hemerythrin-like (H-HxxxE-H-HxxxE); and, (c) metazoan F-box proteins (H-HExxE-H-HxxxE). Interestingly, all but two hemerythrin-like families exhibit internal sequence and structural symmetry, suggesting that a duplication event may have led to the origin of the hemerythrin domain.
Topics: Amino Acid Motifs; Cluster Analysis; Evolution, Molecular; Hemerythrin; Nonheme Iron Proteins; Oxygen; Phylogeny; Protein Domains; Structural Homology, Protein
PubMed: 29330894
DOI: 10.1002/pro.3374 -
Bioinorganic Chemistry and Applications 2022Hemoglobin-based oxygen carriers (HBOCs) have been proposed and tested for several decades for the treatment of hemorrhage. We have previously proposed replacing...
Hemoglobin-based oxygen carriers (HBOCs) have been proposed and tested for several decades for the treatment of hemorrhage. We have previously proposed replacing hemoglobin (Hb) in HBOC with the oxygen-carrying protein hemerythrin (Hr), from marine worms, showing that Hr-based derivatives can perform at least as well or even better than Hb-based HBOC in a range of in vitro assays involving oxidative and nitrosative stress as well as in top-up animal models, where small amounts of Hr- or Hb-HBOC were injected into rats. Here, these experiments are extended to a hemorrhage experiment, in which Hr polymerized with glutaraldehyde, alone or conjugated with human serum albumin, is administered after a loss of 20-30% blood volume. The performance of these preparations is compared with that of Hb-based HBOC measured under the same conditions. Polymerized Hr is found to decrease the survival rate and can hence cannot be used as an oxygen carrier in transfusions. On the other hand, an Hr-albumin copolymer restores survival rates to 100% and generally yields biochemical and histological parameters similar to those of glutaraldehyde-polymerized bovine hemoglobin, with the exception of an acid-base imbalance. The latter may be solved by employing an allogeneic albumin as opposed to the human albumin employed in the present study.
PubMed: 36620348
DOI: 10.1155/2022/2209101 -
Advances in Inorganic Biochemistry 1983
Comparative Study Review
Topics: Animals; Binding Sites; Chemical Phenomena; Chemistry; Hemerythrin; Iron; Metalloproteins; Protein Conformation; Spectrum Analysis
PubMed: 6382960
DOI: No ID Found