2,314 results match your criteria heme-binding

Animal-free heme production for artificial meat in Corynebacterium glutamicum via systems metabolic and membrane engineering.

Metab Eng 2021 May 1. Epub 2021 May 1.

Department of Biotechnology, Korea University, Seoul, 02841, Republic of Korea. Electronic address:

Recently, heme has attracted much attention as a main ingredient that mimics meat flavor in artificial meat in the food industry. Here, we developed Corynebacterium glutamicum capable of high-yield production of heme with systems metabolic engineering and modification of membrane surface. The combination of two precursor pathways based on thermodynamic information increased carbon flux toward heme and porphyrin intermediate biosynthesis. Read More

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Conformational distortion in a fibril-forming oligomer arrests alpha-Synuclein fibrillation and minimizes its toxic effects.

Commun Biol 2021 May 3;4(1):518. Epub 2021 May 3.

Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

The fibrillation pathway of alpha-Synuclein, the causative protein of Parkinson's disease, encompasses transient, heterogeneous oligomeric forms whose structural understanding and link to toxicity are not yet understood. We report that the addition of the physiologically-available small molecule heme at a sub-stoichiometric ratio to either monomeric or aggregated α-Syn, targets a His50 residue critical for fibril-formation and stabilizes the structurally-heterogeneous populations of aggregates into a minimally-toxic oligomeric state. Cryo-EM 3D reconstruction revealed a 'mace'-shaped structure of this monodisperse population of oligomers, which is comparable to a solid-state NMR Greek key-like motif (where the core residues are arranged in parallel in-register sheets with a Greek key topology at the C terminus) that forms the fundamental unit/kernel of protofilaments. Read More

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Linking COVID-19 and Heme-Driven Pathophysiologies: A Combined Computational-Experimental Approach.

Biomolecules 2021 04 27;11(5). Epub 2021 Apr 27.

Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, D-53757 Sankt Augustin, Germany.

The SARS-CoV-2 outbreak was declared a worldwide pandemic in 2020. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes in clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. Read More

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A trio of quinoline-isoniazid-phthalimide with promising antiplasmodial potential: Synthesis, in-vitro evaluation and heme-polymerization inhibition studies.

Bioorg Med Chem 2021 Apr 18;39:116159. Epub 2021 Apr 18.

Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India. Electronic address:

Quinoline-isoniazid-phthalimide triads have been synthesised to assess their antiplasmodial efficacy and cytotoxicity against chloroquine-resistant W2 strain of P. falciparum and Vero cells, respectively. Most of the synthesized compounds displayed IC in lower nM range and appeared to be approximately five to twelve fold more active than chloroquine. Read More

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Heme-binding protein CYB5D1 is a radial spoke component required for coordinated ciliary beating.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, 430072 Wuhan, China;

Coordinated beating is crucial for the function of multiple cilia. However, the molecular mechanism is poorly understood. Here, we characterize a conserved ciliary protein CYB5D1 with a heme-binding domain and a cordon-bleu ubiquitin-like domain. Read More

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Methods for Assessment of Interactions of Proteins with Heme: Application for Complement Proteins and Immunoglobulins.

Methods Mol Biol 2021 ;2227:227-236

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France.

Heme (Fe protoporphyrin IX) serves as a prosthetic group of numerous proteins implicated in oxidative metabolism. This molecule is abundantly present in the red blood cells where it serves as a cofactor of hemoglobin. As consequence of various pathological conditions, the membrane of red blood cells can be damaged and therefore large quantities of hemoglobin and subsequently heme released in the extracellular space. Read More

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January 2021

Soluble MD-2 and Heme in Sickle Cell Disease Plasma Promote Pro-Inflammatory Signaling in Endothelial Cells.

Front Immunol 2021 26;12:632709. Epub 2021 Mar 26.

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.

Recent evidence indicates that hemolysis in sickle cell disease (SCD) promotes inflammation innate immune signaling through toll-like receptor 4 (TLR4). Free heme released by hemolyzed red blood cells can bind to myeloid differentiation factor-2 (MD-2) and activate TLR4 pro-inflammatory signaling on endothelium to promote vaso-occlusion and acute chest syndrome in murine models of SCD. MD-2 is co-expressed with TLR4 on cell membranes, but in inflammatory conditions, soluble MD-2 (sMD-2) is elevated in plasma. Read More

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Catalytic Properties of Flavocytochrome c Sulfide Dehydrogenase from Haloalkaliphilic Bacterium Thioalkalivibrio paradoxus.

Biochemistry (Mosc) 2021 Mar;86(3):361-369

Bach Institute of Biochemistry, Research Centre of Biotechnology, Russian Academy of Sciences, Moscow, 119071, Russia.

Flavocytochrome c sulfide dehydrogenase (FCC) is one of the central enzymes of the respiratory chain in sulfur-oxidizing bacteria. FCC catalyzes oxidation of sulfide and polysulfide ions to elemental sulfur accompanied by electron transfer to cytochrome c. The catalytically active form of the enzyme is a non-covalently linked heterodimer composed of flavin- and heme-binding subunits. Read More

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Transcriptome-based analysis of resistance mechanism to black point caused by Bipolaris sorokiniana in wheat.

Sci Rep 2021 Mar 25;11(1):6911. Epub 2021 Mar 25.

Agronomy College/National Key Laboratory of Wheat and Maize Crop Science, Henan Agricultural University, No. 15 Longzi Lake University Zone, New East District of Zhengzhou, Zhengzhou, 450046, Henan, People's Republic of China.

Black point is a cereal disease caused by complex pathogens, of which the pathogenicity of Bipolaris sorokiniana is the most serious in wheat. Resistance to black point is quantitative in nature, and thus the mechanism is poorly understood. We conducted a comparative transcriptome analysis to identify differentially expressed genes (DEGs) in black point-slightly susceptible and -highly susceptible wheat lines at different timepoints following B. Read More

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Bionoi: A Voronoi Diagram-Based Representation of Ligand-Binding Sites in Proteins for Machine Learning Applications.

Methods Mol Biol 2021 ;2266:299-312

Center for Computation and Technology, Louisiana State University, Baton Rouge, LA, USA.

Bionoi is a new software to generate Voronoi representations of ligand-binding sites in proteins for machine learning applications. Unlike many other deep learning models in biomedicine, Bionoi utilizes off-the-shelf convolutional neural network architectures, reducing the development work without sacrificing the performance. When initially generating images of binding sites, users have the option to color the Voronoi cells based on either one of six structural, physicochemical, and evolutionary properties, or a blend of all six individual properties. Read More

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RNA-seq analysis and gene expression dynamics in the salivary glands of the argasid tick Ornithodoros erraticus along the trophogonic cycle.

Parasit Vectors 2021 Mar 20;14(1):170. Epub 2021 Mar 20.

Parasitología Animal, Instituto de Recursos Naturales y Agrobiología de Salamanca (IRNASA, CSIC), Cordel de Merinas, 40-52, 37008, Salamanca, Spain.

Background: The argasid tick Ornithodoros erraticus is the main vector of tick-borne human relapsing fever (TBRF) and African swine fever (ASF) in the Mediterranean Basin. Tick salivary proteins secreted to the host at the feeding interface play critical roles for tick feeding and may contribute to host infection by tick-borne pathogens; accordingly, these proteins represent interesting antigen targets for the development of vaccines aimed at the control and prevention of tick infestations and tick-borne diseases.

Methods: To identify these proteins, the transcriptome of the salivary glands of O. Read More

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HmuY and Bvu-A Novel Competitive Heme Acquisition Strategy.

Int J Mol Sci 2021 Feb 24;22(5). Epub 2021 Feb 24.

Laboratory of Medical Biology, Faculty of Biotechnology, University of Wrocław, 14A F. Joliot-Curie St., 50-383 Wrocław, Poland.

Human oral and gut microbiomes are crucial for maintenance of homeostasis in the human body. , the key etiologic agent of chronic periodontitis, can cause dysbiosis in the mouth and gut, which results in local and systemic infectious inflammatory diseases. Our previous work resulted in extensive biochemical and functional characterization of one of the major heme acquisition systems (Hmu), with the leading role played by the HmuY hemophore-like protein. Read More

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February 2021

Inhibition of experimental periodontitis by a monoclonal antibody against Porphyromonas gingivalis HA2.

Microb Pathog 2021 Mar 3;154:104633. Epub 2021 Mar 3.

Beijing Institute for Dental Research, Capital Medical University School of Stomatology, China. Electronic address:

It is known that complexes of the multi-protein, gingipain, possess heme binding domains (hemagglutinin 2, HA2) that bind hemoglobin to provide heme and iron to the bacterium, Porphyromonas gingivalis. The DHYAVMISK peptide sequence was proposed to act as an inhibitor of hemin binding, and thus, it might be used to control or prevent periodontal disease. In this study, we created a monoclonal antibody (mAb) that targeted the DHYAVMISK peptide, aimed to determine whether it could inhibit the growth of P. Read More

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IDO1 scavenges reactive oxygen species in myeloid-derived suppressor cells to prevent graft-versus-host disease.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Department of Biomedical Sciences, Seoul National University College of Medicine, Chongno-gu, 03080 Seoul, Korea;

Tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) also has an immunological function to suppress T cell activation in inflammatory circumstances, including graft-versus-host disease (GVHD), a fatal complication after allogeneic bone marrow transplantation (allo-BMT). Although the mononuclear cell expression of IDO1 has been associated with improved outcomes in GVHD, the underlying mechanisms remain unclear. Herein, we used IDO-deficient () BMT to understand why myeloid IDO limits the severity of GVHD. Read More

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Application of proteomics to understand the molecular mechanisms determining meat quality of beef muscles during postmortem aging.

Bin Yang Xuejun Liu

PLoS One 2021 1;16(3):e0246955. Epub 2021 Mar 1.

Jilin Agricultural University, Changchun City, Jilin Province, China.

Proteomics profiling disclosed the molecular mechanism underlying beef poor meat quality. This study aimed to identify protein markers indicating the quality of beef during postmortem storage at 4°C. Beef longissimus dorsi samples were stored at 4°C. Read More

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Binding of the human antioxidation protein α-microglobulin (A1M) to heparin and heparan sulfate. Mapping of binding site, molecular and functional characterization, and co-localization in vivo and in vitro.

Redox Biol 2021 May 10;41:101892. Epub 2021 Feb 10.

Section for Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

Heparin and heparan sulfate (HS) are linear sulfated disaccharide polymers. Heparin is found mainly in mast cells, while heparan sulfate is found in connective tissue, extracellular matrix and on cell membranes in most tissues. α-microglobulin (A1M) is a ubiquitous protein with thiol-dependent antioxidant properties, protecting cells and matrix against oxidative damage due to its reductase activities and radical- and heme-binding properties. Read More

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REV-ERB Agonist SR9009 Regulates the Proliferation and Neurite Outgrowth/Suppression of Cultured Rat Adult Hippocampal Neural Stem/Progenitor Cells in a Concentration-Dependent Manner.

Koji Shimozaki

Cell Mol Neurobiol 2021 Feb 18. Epub 2021 Feb 18.

Division of Functional Genomics, Life Science Support Center, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523, Japan.

REV-ERBs are heme-binding nuclear receptors that regulate the circadian rhythm and play important roles in the regulation of proliferation and the neuronal differentiation process in neuronal stem/progenitor cells in the adult brain. However, the effects of REV-ERB activation in the adult brain remain unclear. In this study, SR9009, a synthetic REV-ERB agonist that produces anxiolytic effects in mice, was used to treat undifferentiated and neuronally differentiated cultured rat adult hippocampal neural stem/progenitor cells (AHPs). Read More

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February 2021

Identification of Potential Biomarkers and Immune Infiltration Characteristics in Idiopathic Pulmonary Arterial Hypertension Using Bioinformatics Analysis.

Front Cardiovasc Med 2021 1;8:624714. Epub 2021 Feb 1.

Department of Structural Heart Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but severe lung disorder, which may lead to heart failure and early mortality. However, little is known about the etiology of IPAH. Thus, the present study aimed to establish the differentially expressed genes (DEGs) between IPAH and normal tissues, which may serve as potential prognostic markers in IPAH. Read More

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February 2021

Genome-wide identification and gene-editing of pigment transporter genes in the swallowtail butterfly Papilio xuthus.

BMC Genomics 2021 Feb 17;22(1):120. Epub 2021 Feb 17.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China.

Background: Insect body coloration often functions as camouflage to survive from predators or mate selection. Transportation of pigment precursors or related metabolites from cytoplasm to subcellular pigment granules is one of the key steps in insect pigmentation and usually executed via such transporter proteins as the ATP-binding cassette (ABC) transmembrane transporters and small G-proteins (e.g. Read More

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February 2021

The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease.

Front Immunol 2020 27;11:561917. Epub 2021 Jan 27.

Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Hemolysis is a pathological feature of several diseases of diverse etiology such as hereditary anemias, malaria, and sepsis. A major complication of hemolysis involves the release of large quantities of hemoglobin into the blood circulation and the subsequent generation of harmful metabolites like labile heme. Protective mechanisms like haptoglobin-hemoglobin and hemopexin-heme binding, and heme oxygenase-1 enzymatic degradation of heme limit the toxicity of the hemolysis-related molecules. Read More

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Revisiting the interaction of heme with hemopexin.

Biol Chem 2021 May 19;402(6):675-691. Epub 2021 Feb 19.

Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121Bonn, Germany.

In hemolytic disorders, erythrocyte lysis results in massive release of hemoglobin and, subsequently, toxic heme. Hemopexin is the major protective factor against heme toxicity in human blood and currently considered for therapeutic use. It has been widely accepted that hemopexin binds heme with extraordinarily high affinity of <1 pM in a 1:1 ratio. Read More

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Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ.

Sci Adv 2021 Jan 27;7(5). Epub 2021 Jan 27.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.

Heme is the endogenous ligand for the constitutively repressive REV-ERB nuclear receptors, REV-ERBα (NR1D1) and REV-ERBβ (NR1D2), but how heme regulates REV-ERB activity remains unclear. Cellular studies indicate that heme is required for the REV-ERBs to bind the corepressor NCoR and repress transcription. However, fluorescence-based biochemical assays suggest that heme displaces NCoR; here, we show that this is due to a heme-dependent artifact. Read More

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January 2021

Azole-Based Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

J Med Chem 2021 02 8;64(4):2205-2227. Epub 2021 Feb 8.

Molecular Modeling Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.

The heme enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays an essential role in immunity, neuronal function, and aging through catalysis of the rate-limiting step in the kynurenine pathway of tryptophan metabolism. Many IDO1 inhibitors with different chemotypes have been developed, mainly targeted for use in anti-cancer immunotherapy. Lead optimization of direct heme iron-binding inhibitors has proven difficult due to the remarkable selectivity and sensitivity of the heme-ligand interactions. Read More

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February 2021

-Designed β-Sheet Heme Proteins.

Biochemistry 2021 Feb 3;60(6):431-439. Epub 2021 Feb 3.

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.

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. Read More

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February 2021

A High-Throughput Method for Identifying Novel Genes That Influence Metabolic Pathways Reveals New Iron and Heme Regulation in Pseudomonas aeruginosa.

mSystems 2021 Feb 2;6(1). Epub 2021 Feb 2.

Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA

Heme is an essential metabolite for most life on earth. Bacterial pathogens almost universally require iron to infect a host, often acquiring this nutrient in the form of heme. The Gram-negative pathogen is no exception, where heme acquisition and metabolism are known to be crucial for both chronic and acute infections. Read More

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February 2021

Human Plasma and Recombinant Hemopexins: Heme Binding Revisited.

Int J Mol Sci 2021 Jan 26;22(3). Epub 2021 Jan 26.

Department of Pathology, The University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin (the term "heme" is used in this article to denote both the ferrous and ferric forms). During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. Read More

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January 2021

Pushing and Pulling: A Dual pH Trigger Controlled by Varying the Alkyl Tail Length in Heme Coordinating Peptide Amphiphiles.

J Phys Chem B 2021 02 2;125(5):1317-1330. Epub 2021 Feb 2.

Pritzker School of Molecular Engineering, University of Chicago, 5640 South Ellis Avenue, Chicago, Illinois 60637, United States.

Some organisms in nature that undergo anaerobic respiration utilize 1D nanoscale arrays of densely packed cytochromes containing the molecule heme. The assemblies can be mimicked with 1D nanoscale fibrils composed of peptide amphiphiles designed to coordinate heme in dense arrays. To create such materials and assemblies, it is critical to understand the assembly process and what controls the various aspects of hierarchical assembly. Read More

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February 2021

Linking Labile Heme with Thrombosis.

J Clin Med 2021 Jan 22;10(3). Epub 2021 Jan 22.

Pharmaceutical Biochemistry and Bioanalytics, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.

Thrombosis is one of the leading causes of death worldwide. As such, it also occurs as one of the major complications in hemolytic diseases, like hemolytic uremic syndrome, hemorrhage and sickle cell disease. Under these conditions, red blood cell lysis finally leads to the release of large amounts of labile heme into the vascular compartment. Read More

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January 2021

Heme Binding to HupZ with a C-Terminal Tag from Group A Streptococcus.

Molecules 2021 Jan 21;26(3). Epub 2021 Jan 21.

Department of Chemistry, The University of Texas at San Antonio, San Antonio, TX 78249, USA.

HupZ is an expected heme degrading enzyme in the heme acquisition and utilization pathway in Group A Streptococcus. The isolated HupZ protein containing a C-terminal V5-His tag exhibits a weak heme degradation activity. Here, we revisited and characterized the HupZ-V5-His protein via biochemical, mutagenesis, protein quaternary structure, UV-vis, EPR, and resonance Raman spectroscopies. Read More

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January 2021

NEAr Transporter (NEAT) Domains: Unique Surface Displayed Heme Chaperones That Enable Gram-Positive Bacteria to Capture Heme-Iron From Hemoglobin.

Front Microbiol 2020 6;11:607679. Epub 2021 Jan 6.

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, United States.

Iron is an important micronutrient that is required by bacteria to proliferate and to cause disease. Many bacterial pathogens forage iron from human hemoglobin (Hb) during infections, which contains this metal within heme (iron-protoporphyrin IX). Several clinically important pathogenic species within the Firmicutes phylum scavenge heme using surface-displayed or secreted NEAr Transporter (NEAT) domains. Read More

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January 2021