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Trends in Immunology Aug 2023PANoptosomes are large cell death-inducing complexes that drive a type of cell death called PANoptosis during infection and inflammation. Sundaram and colleagues...
PANoptosomes are large cell death-inducing complexes that drive a type of cell death called PANoptosis during infection and inflammation. Sundaram and colleagues recently identified NLRP12 as a PANoptosome that induces PANoptosis in response to heme, TNF, and pathogen-associated molecular patterns (PAMPs), indicating a role for NLRP12 in hemolytic and inflammatory diseases.
Topics: Humans; Intracellular Signaling Peptides and Proteins; Heme; Inflammation
PubMed: 37423881
DOI: 10.1016/j.it.2023.06.008 -
Current Opinion in Structural Biology Dec 2019Mechanisms for making and breaking the heme b cofactor (heme) are more diverse than previously expected. Biosynthetic pathways have diverged at least twice along... (Review)
Review
Mechanisms for making and breaking the heme b cofactor (heme) are more diverse than previously expected. Biosynthetic pathways have diverged at least twice along taxonomic lines, reflecting differences in membrane organization and O utilization among major groups of organisms. At least three families of heme degradases are now known, again differing in whether and how O is used by the organism and possibly the purpose for turning over the tetrapyrrole. Understanding these enzymes and pathways offers a handle for antimicrobial development and for monitoring heme use in organismal and ecological systems.
Topics: Binding Sites; Catalytic Domain; Heme; Metabolic Networks and Pathways; Models, Molecular; Molecular Conformation; Molecular Structure; Oxidation-Reduction; Protein Binding; Quantitative Structure-Activity Relationship; Sensitivity and Specificity
PubMed: 30802830
DOI: 10.1016/j.sbi.2019.01.006 -
Journal of Inorganic Biochemistry Jan 2024
Topics: Heme
PubMed: 37953207
DOI: 10.1016/j.jinorgbio.2023.112423 -
Biochemistry Feb 2021The field of protein design has met with considerable success over the past few decades. Heme, a cofactor, has often been introduced to impart a diverse array of... (Review)
Review
The field of protein design has met with considerable success over the past few decades. Heme, a cofactor, has often been introduced to impart a diverse array of functions to a protein, ranging from electron transport to respiration. In nature, heme is found to occur predominantly in α-helical structures over β-sheets, which has resulted in significant designs of heme proteins utilizing coiled-coil helices. By contrast, there are only a few known β-sheet proteins that bind heme and designs of β-sheets frequently result in amyloid-like aggregates. This review reflects on our success in designing a series of multistranded β-sheet heme binding peptides that are well folded in both aqueous and membrane-like environments. Initially, we designed a β-hairpin peptide that self-assembles to bind heme and performs peroxidase activity in membrane. The β-hairpin was optimized further to accommodate a heme binding pocket within multistranded β-sheets for catalysis and electron transfer in membranes. Furthermore, we designed and characterized β-sheet peptides and miniproteins that are soluble in an aqueous environment capable of binding single and multiple hemes with high affinity and stability. Collectively, these studies highlight the substantial progress made toward the design of functional β-sheets.
Topics: Amino Acid Sequence; Circular Dichroism; Heme; Hemeproteins; Oxidation-Reduction; Peptides; Protein Conformation, beta-Strand; Protein Engineering; Protein Folding; Protein Structure, Secondary
PubMed: 33533248
DOI: 10.1021/acs.biochem.0c00662 -
Biological Reviews of the Cambridge... Feb 2022The capacity of haem to transfer electrons, bind diatomic gases, and catalyse various biochemical reactions makes it one of the essential biomolecules on Earth and one... (Review)
Review
The capacity of haem to transfer electrons, bind diatomic gases, and catalyse various biochemical reactions makes it one of the essential biomolecules on Earth and one that was likely used by the earliest forms of cellular life. Since the description of haem biosynthesis, our understanding of this multi-step pathway has been almost exclusively derived from a handful of model organisms from narrow taxonomic contexts. Recent advances in genome sequencing and functional studies of diverse and previously neglected groups have led to discoveries of alternative routes of haem biosynthesis that deviate from the 'classical' pathway. In this review, we take an evolutionarily broad approach to illuminate the remarkable diversity and adaptability of haem synthesis, from prokaryotes to eukaryotes, showing the range of strategies that organisms employ to obtain and utilise haem. In particular, the complex evolutionary histories of eukaryotes that involve multiple endosymbioses and horizontal gene transfers are reflected in the mosaic origin of numerous metabolic pathways with haem biosynthesis being a striking case. We show how different evolutionary trajectories and distinct life strategies resulted in pronounced tensions and differences in the spatial organisation of the haem biosynthesis pathway, in some cases leading to a complete loss of a haem-synthesis capacity and, rarely, even loss of a requirement for haem altogether.
Topics: Biological Evolution; Eukaryota; Heme; Metabolic Networks and Pathways
PubMed: 34472688
DOI: 10.1111/brv.12794 -
Annual Review of Medicine Jan 2024Carbon monoxide (CO) poisoning leads to 50,000-100,000 emergency room visits and 1,500-2,000 deaths each year in the United States alone. Even with treatment, survivors... (Review)
Review
Carbon monoxide (CO) poisoning leads to 50,000-100,000 emergency room visits and 1,500-2,000 deaths each year in the United States alone. Even with treatment, survivors often suffer from long-term cardiac and neurocognitive deficits, highlighting a clear unmet medical need for novel therapeutic strategies that reduce morbidity and mortality associated with CO poisoning. This review examines the prevalence and impact of CO poisoning and pathophysiology in humans and highlights recent advances in therapeutic strategies that accelerate CO clearance and mitigate toxicity. We focus on recent developments of high-affinity molecules that take advantage of the uniquely strong interaction between CO and heme to selectively bind and sequester CO in preclinical models. These scavengers, which employ heme-binding scaffolds ranging from organic small molecules to hemoproteins derived from humans and potentially even microorganisms, show promise as field-deployable antidotes that may rapidly accelerate CO clearance and improve outcomes for survivors of acute CO poisoning.
Topics: Humans; United States; Carbon Monoxide Poisoning; Heme
PubMed: 37582490
DOI: 10.1146/annurev-med-052422-020045 -
Blood Sep 2021
Topics: Erythrocytes; Heme
PubMed: 34591096
DOI: 10.1182/blood.2021012875 -
Trends in Plant Science Sep 2021Nitric oxide (NO) sensing is an ancient trait enabled by hemoproteins harboring a highly conserved Heme-Nitric oxide/OXygen (H-NOX) domain that operates throughout... (Review)
Review
Nitric oxide (NO) sensing is an ancient trait enabled by hemoproteins harboring a highly conserved Heme-Nitric oxide/OXygen (H-NOX) domain that operates throughout bacteria, fungi, and animal kingdoms including in humans, but that has long thought to be absent in plants. Recently, H-NOX-containing plant hemoproteins mediating crucial NO-dependent responses such as stomatal closure and pollen tube guidance have been reported. There are indications that the detection method that led to these discoveries will uncover many more heme-based NO sensors that operate as regulatory sites in complex proteins. Their characterizations will in turn offer a much more complete picture of plant NO responses at both the molecular and systems level.
Topics: Heme; Hemeproteins; Nitric Oxide; Oxygen; Plant Physiological Phenomena
PubMed: 33867269
DOI: 10.1016/j.tplants.2021.03.009 -
Biological Chemistry Nov 2022Heme (protoheme IX) is an essential cofactor for a large variety of proteins whose functions vary from one electron reactions to binding gases. While not ubiquitous,... (Review)
Review
Heme (protoheme IX) is an essential cofactor for a large variety of proteins whose functions vary from one electron reactions to binding gases. While not ubiquitous, heme is found in the great majority of known life forms. Unlike most cofactors that are acquired from dietary sources, the vast majority of organisms that utilize heme possess a complete pathway to synthesize the compound. Indeed, dietary heme is most frequently utilized as an iron source and not as a source of heme. In Nature there are now known to exist three pathways to synthesize heme. These are the siroheme dependent (SHD) pathway which is the most ancient, but least common of the three; the coproporphyrin dependent (CPD) pathway which with one known exception is found only in gram positive bacteria; and the protoporphyrin dependent (PPD) pathway which is found in gram negative bacteria and all eukaryotes. All three pathways share a core set of enzymes to convert the first committed intermediate, 5-aminolevulinate (ALA) into uroporphyrinogen III. In the current review all three pathways are reviewed as well as the two known pathways to synthesize ALA. In addition, interesting features of some heme biosynthesis enzymes are discussed as are the regulation and disorders of heme biosynthesis.
Topics: Heme; Aminolevulinic Acid; Iron
PubMed: 36029525
DOI: 10.1515/hsz-2022-0205 -
Chemistry, An Asian Journal Apr 2021A series of bis-acryl functionalized porphyrins and their corresponding metalloporphyrins (M=Co, Mn) were synthesized and investigated for their antimicrobial properties...
A series of bis-acryl functionalized porphyrins and their corresponding metalloporphyrins (M=Co, Mn) were synthesized and investigated for their antimicrobial properties through MIC screening and bacteria time-kill kinetic studies. The Mn(III) 4-(bis)methylphenyl-substituted-porphyrins showed superior batericidal activities even in the dark with low hemotoxicity and good cytotoxicity profile.
Topics: Anti-Bacterial Agents; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Escherichia coli; Hemolysis; Humans; Kinetics; Metalloporphyrins; Molecular Structure; Staphylococcus aureus
PubMed: 33617127
DOI: 10.1002/asia.202100053