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Biomolecular Concepts May 2017Classical all α-helical globins are present in all living organisms and are ordered in three lineages: (i) flavohemoglobins and single domain globins, (ii) protoglobins... (Review)
Review
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 heme-based 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 α1-microglobulin (α1-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 α1-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-α1-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.
Topics: Animals; Bedbugs; Hemeproteins; Humans; Kinetics; Models, Molecular; Protein Structure, Tertiary; Salivary Proteins and Peptides; Thermodynamics
PubMed: 28574374
DOI: 10.1515/bmc-2017-0013 -
The Journal of Biological Chemistry May 2013Heme is a prosthetic group best known for roles in oxygen transport, oxidative catalysis, and respiratory electron transport. Recent years have seen the roles of heme... (Review)
Review
Heme is a prosthetic group best known for roles in oxygen transport, oxidative catalysis, and respiratory electron transport. Recent years have seen the roles of heme extended to sensors of gases such as O2 and NO and cell redox state, and as mediators of cellular responses to changes in intracellular levels of these gases. The importance of heme is further evident from identification of proteins that bind heme reversibly, using it as a signal, e.g. to regulate gene expression in circadian rhythm pathways and control heme synthesis itself. In this minireview, we explore the current knowledge of the diverse roles of heme sensor proteins.
Topics: Animals; Carbon Monoxide; Circadian Rhythm; Gene Expression Regulation; Guanylate Cyclase; Heme; Hemeproteins; Homeostasis; Humans; Oxidation-Reduction; Oxidative Stress; Oxygen
PubMed: 23539616
DOI: 10.1074/jbc.R112.422642 -
The Journal of Biological Chemistry Apr 2024Heme is an iron-containing prosthetic group necessary for the function of several proteins termed "hemoproteins." Erythrocytes contain most of the body's heme in the... (Review)
Review
Heme is an iron-containing prosthetic group necessary for the function of several proteins termed "hemoproteins." Erythrocytes contain most of the body's heme in the form of hemoglobin and contain high concentrations of free heme. In nonerythroid cells, where cytosolic heme concentrations are 2 to 3 orders of magnitude lower, heme plays an essential and often overlooked role in a variety of cellular processes. Indeed, hemoproteins are found in almost every subcellular compartment and are integral in cellular operations such as oxidative phosphorylation, amino acid metabolism, xenobiotic metabolism, and transcriptional regulation. Growing evidence reveals the participation of heme in dynamic processes such as circadian rhythms, NO signaling, and the modulation of enzyme activity. This dynamic view of heme biology uncovers exciting possibilities as to how hemoproteins may participate in a range of physiologic systems. Here, we discuss how heme is regulated at the level of its synthesis, availability, redox state, transport, and degradation and highlight the implications for cellular function and whole organism physiology.
Topics: Animals; Humans; Circadian Rhythm; Heme; Hemeproteins; Oxidation-Reduction; Signal Transduction; Intracellular Space; Cell Physiological Phenomena
PubMed: 38432636
DOI: 10.1016/j.jbc.2024.107132 -
Journal of Inorganic Biochemistry Sep 2021Heme enzymes are some of the most versatile catalysts in nature. In recent years it has been found that they can also catalyze reactions for which there are no... (Review)
Review
Heme enzymes are some of the most versatile catalysts in nature. In recent years it has been found that they can also catalyze reactions for which there are no equivalents in nature. This development has been driven by the abiological catalytic reactivity reported for bio-inspired and biomimetic iron porphyrin complexes. This review focuss es on heme enzymes for catalysis of cyclopropanation reactions. The two most important approaches used to create enzymes for cyclopropanation are repurposing of heme enzymes and the various strategies used to improve these enzymes such as mutagenesis and heme replacement, and artificial heme enzymes. These strategies are introduced and compared. Moreover, lessons learned with regard to mechanism and design principles are discussed.
Topics: Biocatalysis; Cyclopropanes; DNA; Enzymes; G-Quadruplexes; Heme; Hemeproteins; Mutation; Protein Engineering
PubMed: 34217039
DOI: 10.1016/j.jinorgbio.2021.111523 -
Current Opinion in Biotechnology Jun 2021Hemoprotein-catalyzed carbene and nitrene transformations have emerged as powerful tools for constructing complex molecules; they also nicely illustrate how new protein... (Review)
Review
Hemoprotein-catalyzed carbene and nitrene transformations have emerged as powerful tools for constructing complex molecules; they also nicely illustrate how new protein catalysts can emerge, evolve and diversify. These laboratory-invented enzymes exploit the ability of proteins to tame highly reactive carbene and nitrene species and direct their fates with high selectivity. New-to-nature carbene and nitrene transferases catalyze many useful reactions, including some that have no precedent using chemical methods. Here we cover recent advances in this field, including alkyne cyclopropenation, arene cyclopropanation, carbene CH insertion, intramolecular nitrene CH insertion, alkene aminohydroxylation, and primary amination. For such transformations, biocatalysts have exceeded the performance of reported small-molecule catalysts in terms of selectivity and catalyst turnovers. Finally, we offer our thoughts on using these new enzymatic reactions in chemical synthesis, integrating them into biological pathways and chemo-enzymatic cascades, and on their current limitations.
Topics: Hemeproteins; Imines; Methane; Transferases
PubMed: 33370622
DOI: 10.1016/j.copbio.2020.12.005 -
Biomolecules Apr 2023Hemoproteins include several heme-binding proteins with distinct structure and function. The presence of the heme group confers specific reactivity and spectroscopic... (Review)
Review
Hemoproteins include several heme-binding proteins with distinct structure and function. The presence of the heme group confers specific reactivity and spectroscopic properties to hemoproteins. In this review, we provide an overview of five families of hemoproteins in terms of dynamics and reactivity. First, we describe how ligands modulate cooperativity and reactivity in globins, such as myoglobin and hemoglobin. Second, we move on to another family of hemoproteins devoted to electron transport, such as cytochromes. Later, we consider heme-based reactivity in hemopexin, the main heme-scavenging protein. Then, we focus on heme-albumin, a chronosteric hemoprotein with peculiar spectroscopic and enzymatic properties. Eventually, we analyze the reactivity and dynamics of the most recently discovered family of hemoproteins, i.e., nitrobindins.
Topics: Heme; Ligands; Hemeproteins
PubMed: 37189430
DOI: 10.3390/biom13040683 -
Archives of Biochemistry and Biophysics Jul 2021Oxo-bridged diiron proteins are a distinct class of non-heme iron proteins. Their active sites are composed of two irons that are coordinated by amino acid side chains,... (Review)
Review
Oxo-bridged diiron proteins are a distinct class of non-heme iron proteins. Their active sites are composed of two irons that are coordinated by amino acid side chains, and a bridging oxygen that interacts with each iron. These proteins are members of the ferritin superfamily and share the structural feature of a four α-helix bundle that provides the residues that coordinate the irons. The different proteins also display a wide range of structures and functions. A prototype of this family is hemerythrin, which functions as an oxygen transporter. Several other hemerythrin-like proteins have been described with a diversity of functions including oxygen and iron sensing, and catalytic activities. Rubrerythrins react with hydrogen peroxide and rubrerythrin-like proteins possess a rubredoxin domain, in addition to the oxo-bridged diiron center. Other redox enzymes with oxo-bridged irons include flavodiiron proteins that act as O or NO reductases, ribonucleotide reductase and methane monooxygenase. Ferritins have an oxo-bridged diiron in the ferroxidase center of the protein, which plays a role in the iron storage function of these proteins. There are also bacterial ferritins that exhibit catalytic activities. The structures and functions of this broad class of oxo-bridged diiron proteins are described and compared in this review.
Topics: Hemeproteins; Iron; Models, Molecular; Oxygen; Protein Conformation
PubMed: 33991497
DOI: 10.1016/j.abb.2021.108917 -
Antioxidants & Redox Signaling Apr 2014Heme degradation, which was described more than 30 years ago, is still very actively explored with many novel discoveries on its role in various disease models every... (Review)
Review
SIGNIFICANCE
Heme degradation, which was described more than 30 years ago, is still very actively explored with many novel discoveries on its role in various disease models every year.
RECENT ADVANCES
The heme oxygenases (HO) are metabolic enzymes that utilize NADPH and oxygen to break apart the heme moiety liberating biliverdin (BV), carbon monoxide (CO), and iron. Heme that is derived from hemoproteins can be toxic to the cells and if not removed immediately, it causes cell apoptosis and local inflammation. Elimination of heme from the milieu enables generation of three products that influences numerous metabolic changes in the cell.
CRITICAL ISSUES
CO has profound effects on mitochondria and cellular respiration and other hemoproteins to which it can bind and affect their function, while BV and bilirubin (BR), the substrate and product of BV, reductase, respectively, are potent antioxidants. Sequestration of iron into ferritin and its recycling in the tissues is a part of the homeodynamic processes that control oxidation-reduction in cellular metabolism. Further, heme is an important component of a number of metabolic enzymes, and, therefore, HO-1 plays an important role in the modulation of cellular bioenergetics.
FUTURE DIRECTIONS
In this review, we describe the cross-talk between heme oxygenase-1 (HO-1) and its products with other metabolic pathways. HO-1, which we have labeled Nike, the goddess who personified victory, dictates triumph over pathophysiologic conditions, including diabetes, ischemia, and cancer.
Topics: Animals; Biosynthetic Pathways; Carbon Monoxide; Cell Respiration; Diabetes Mellitus; Heme; Heme Oxygenase-1; Hemeproteins; Humans; Iron; Mitochondria; Neoplasms
PubMed: 24180257
DOI: 10.1089/ars.2013.5667 -
DNA and Cell Biology Apr 2002Biological systems rely on heme-proteins to carry out a number of basic functions essential for their survival. Hemes, or iron-porphyrin complexes, are the versatile and... (Review)
Review
Biological systems rely on heme-proteins to carry out a number of basic functions essential for their survival. Hemes, or iron-porphyrin complexes, are the versatile and ubiquitous active centers of these proteins. In the past decade, discovery of new heme-proteins, together with functional and structural research, provided a wealth of information on these diverse and biologically important molecules. Structure determination work has shown that nature has used a variety of different scaffolds and architectures to bind heme and modulate functions such as redox properties. Structural data have also provided insights into the heme-linked protein conformational changes required in many regulatory heme-proteins. Remarkable efforts have been made towards the understanding of factors governing redox potentials. Site-directed mutagenesis studies and theoretical calculations on heme environments investigated the roles of hydrophobic and electrostatic residues, and analyzed the effect of heme solvent accessibility. This review focuses on the structure-function relationships underlying the association of heme in signaling and iron metabolism proteins. In addition, an account is given about molecular features affecting heme's redox properties; this briefly revisits previous conclusions in the light of some more recent reports.
Topics: Animals; Hemeproteins; Humans; Oxidation-Reduction; Structure-Activity Relationship
PubMed: 12042067
DOI: 10.1089/104454902753759690 -
IUBMB Life Jan 2008Flavohemoglobins (flavoHbs) are made of a globin domain fused with a ferredoxin reductaselike FAD- and NAD-binding modules. These proteins are widely represented among... (Review)
Review
Flavohemoglobins (flavoHbs) are made of a globin domain fused with a ferredoxin reductaselike FAD- and NAD-binding modules. These proteins are widely represented among bacteria and yeasts and represent a most challenging research subject in view of their high reactivity both as reductases and as oxidases. The functional annotations of flavoHbs are still controversial, and different physiological roles that are linked to cell responses to oxidative and/or nitrosative stress have been proposed. The flavoHb from Escherichia coli (HMP) has been the object of a large number of investigations to unveil its physiological role in the framework of bacterial resistance to nitrosative stress. HMP expression has been demonstrated to respond to the presence of NO in the culture medium, and an explicit mechanism has been proposed that involves NO scavenging and its reduction to N(2)O under anaerobic conditions. In contrast to (or together with) the anaerobic NO-reductase activity, HMP has also been shown to be able to catalyze the oxidation of NO to NO(3) (-) (NO-dioxygenase activity) both in vivo and in vitro in the presence of O(2) and NADH. HMP has also been shown to be capable of catalyzing the reduction of several alkylhydroperoxide substrates into their corresponding alcohols using NADH as an electron donor. The alkylhydroperoxide reductase activity taken together with the unique lipid-binding properties of HMP suggests that this flavoHb may be involved in the repair of the lipid membrane oxidative damage generated during oxidative/nitrosative stress.
Topics: Amino Acid Sequence; Bacterial Proteins; Binding Sites; Escherichia coli Proteins; Ferric Compounds; Ferrous Compounds; Hemeproteins; Ligands; Models, Molecular; Oxidoreductases; Oxygenases; Peroxiredoxins; Protein Structure, Tertiary
PubMed: 18379989
DOI: 10.1002/iub.9