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https://www.readbyqxmd.com/read/28443661/engineering-of-rumb-toward-a-green-catalyst-for-carbene-insertion-reactions
#1
Matthew W Wolf, David A Vargas, Nicolai Lehnert
The small, stable heme protein myoglobin (Mb) was modified through cofactor substitution and mutagenesis to develop a new catalyst for carbene transfer reactions. The native heme was removed from wild-type Mb and several Mb His64 mutants (H64D, H64A, H64V), and the resulting apoproteins were reconstituted with ruthenium mesoporphyrin IX (RuMpIX). The reconstituted proteins (RuMb) were characterized by UV-vis and circular dichroism spectroscopy and were used as catalysts for the N-H insertion of aniline derivatives and the cyclopropanation of styrene derivatives...
April 26, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28443478/role-of-oxidative-stress-in-epigenetic-modification-in-endometriosis
#2
Fuminori Ito, Yuki Yamada, Aiko Shigemitsu, Mika Akinishi, Hiroko Kaniwa, Ryuta Miyake, Shoichiro Yamanaka, Hiroshi Kobayashi
Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28436221/the-iron-chaperone-protein-cyay-from-vibrio-cholerae-is-a-heme-binding-protein
#3
Takeshi Uchida, Noriyuki Kobayashi, Souichiro Muneta, Koichiro Ishimori
CyaY is an iron transport protein for Fe-S cluster biosynthetic systems and a ferrochelatase that catalyzes insertion of Fe(2+) into protoporphyrin IX. Here, we found that CyaY has the ability to bind heme as well as iron, exhibiting a dissociation constant for heme of 21 ± 6 nM. Absorption and resonance Raman spectra revealed that both ferric and ferrous forms of heme were bound to an anionic ligand (e.g., tyrosine and/or cysteine). Consistent with this, mutagenesis studies showed that Tyr67 and Cys78 are possible heme ligands of CyaY...
April 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28433686/mitochatting-if-only-we-could-be-a-fly-on-the-cell-wall
#4
REVIEW
Michal Eisenberg-Bord, Maya Schuldiner
Mitochondria, cellular metabolic hubs, perform many essential processes and are required for the production of metabolites such as ATP, iron-sulfur clusters, heme, amino acids and nucleotides. To fulfill their multiple roles, mitochondria must communicate with all other organelles to exchange small molecules, ions and lipids. Since mitochondria are largely excluded from vesicular trafficking routes, they heavily rely on membrane contact sites. Contact sites are areas of close proximity between organelles that allow efficient transfer of molecules, saving the need for slow and untargeted diffusion through the cytosol...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28433662/iron-and-thiol-redox-signaling-in-cancer-an-exquisite-balance-to-escape-ferroptosis
#5
REVIEW
Shinya Toyokuni, Fumiya Ito, Kyoko Yamashita, Yasumasa Okazaki, Shinya Akatsuka
Epidemiological data indicate a constant worldwide increase in cancer mortality, although the age of onset is increasing. Recent accumulation of genomic data on human cancer via next-generation sequencing confirmed that cancer is a disease of genome alteration. In many cancers, the Nrf2 transcription system is activated via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent activation of the genes with antioxidative functions. Furthermore, deep sequencing of passenger mutations is clarifying responsible cancer causative agent(s) in each case, including aging, APOBEC activation, smoking and UV...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433637/inhibition-of-pro-inflammatory-enzymes-by-medicinal-plants-from-the-argentinean-highlands-puna
#6
Romina Torres-Carro, María Inés Isla, Samanta Thomas-Valdes, Felipe Jiménez-Aspee, Guillermo Schmeda-Hirschmann, María Rosa Alberto
ETHNOPHARMACOLOGICAL RELEVANCE: Human groups in the Argentinean Andes highlands (Puna) selected native plants as anti-inflammatory agents. The indications of use are mainly to relieve pain, in infusions, ethanolic extracts or plasters. AIM OF THE STUDY: The objective of the study was to assess the effect of hydroalcoholic extracts from native highland plants as anti-inflammatory according to the traditional indications of use. The chemical profile of the three most active species was analyzed by HPLC-ESI-MS to get in insight into the constituents and the effects observed, according to the ethnopharmacological information...
April 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28426768/abundance-of-the-iron-containing-biomolecule-heme-b-during-the-progression-of-a-spring-phytoplankton-bloom-in-a-mesocosm-experiment
#7
Jessica Bellworthy, Martha Gledhill, Mario Esposito, Eric P Achterberg
Concentrations of heme b were determined in a mesocosm experiment situated in Gullmar Fjord off Sweden. The mesocosm experiment lasted for ca. one hundred days and was characterised by the growth of a primary nutrient replete and a secondary nutrient deplete phytoplankton bloom. Heme b varied between 40 ± 10 pmol L-1 in the prebloom period up to a maximum of 700 ± 400 pmol L-1 just prior to the time of the primary chlorophyll a maximum. Thereafter, heme b concentrations decreased again to an average of 120 ± 60 pmol L-1...
2017: PloS One
https://www.readbyqxmd.com/read/28426718/effects-of-dietary-beef-pork-chicken-and-salmon-on-intestinal-carcinogenesis-in-a-j-min-mice
#8
Christina Steppeler, Marianne Sødring, Bjørg Egelandsdal, Bente Kirkhus, Marije Oostindjer, Ole Alvseike, Lars Erik Gangsei, Ellen-Margrethe Hovland, Fabrice Pierre, Jan Erik Paulsen
The International Agency for Research on Cancer has classified red meat as "probably carcinogenic to humans" (Group 2A). In mechanistic studies exploring the link between intake of red meat and CRC, heme iron, the pigment of red meat, is proposed to play a central role as a catalyzer of luminal lipid peroxidation and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle food (dry weight) and 60% powder diet) on Apc-driven intestinal carcinogenesis, from week 3-13 of age...
2017: PloS One
https://www.readbyqxmd.com/read/28426241/extracellular-heme-uptake-and-the-challenge-of-bacterial-cell-membranes
#9
Weiliang Huang, Angela Wilks
Iron is essential for the survival of most bacteria but presents a significant challenge given its limited bioavailability. Furthermore, the toxicity of iron combined with the need to maintain physiological iron levels within a narrow concentration range requires sophisticated systems to sense, regulate, and transport iron. Most bacteria have evolved mechanisms to chelate and transport ferric iron (Fe(3+)) via siderophore receptor systems, and pathogenic bacteria have further lowered this barrier by employing mechanisms to utilize the host's hemoproteins...
April 19, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28424608/blood-transcriptomic-meta-analysis-identifies-dysregulation-of-hemoglobin-and-iron-metabolism-in-parkinson-disease
#10
Jose A Santiago, Judith A Potashkin
Disrupted iron metabolism has been implicated in the pathogenesis of Parkinson's disease (PD), a progressive neurodegenerative disorder that severely affects movement and coordination, yet the molecular mechanisms underlying this association remain unknown. To this end, we performed a transcriptomic meta-analysis of four blood microarrays in PD. We observed a significant downregulation of genes related to hemoglobin including, hemoglobin delta (HBD), alpha hemoglobin stabilizing protein (ASHP), genes implicated in iron metabolism including, solute carrier family 11 member 2 (SLC11A2), ferrochelatase (FECH), and erythrocyte-specific genes including erythrocyte membrane protein (EPB42), and 5'-aminolevulinate synthase 2 (ALAS2)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28421060/the-heme-metabolite-carbon-monoxide-facilitates-kshv-infection-by-inhibiting-tlr4-signaling-in-endothelial-cells
#11
Sara Botto, Jean K Gustin, Ashlee V Moses
Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi sarcoma (KS) and certain rare B cell lymphoproliferative disorders. KSHV infection of endothelial cells (EC) in vitro increases expression of the inducible host-encoded enzyme heme oxygenase-1 (HO-1), which is also strongly expressed in KS tumors. HO-1 catalyzes the rate-limiting step in the conversion of heme into iron, biliverdin and the gasotransmitter carbon monoxide (CO), all of which share anti-apoptotic, anti-inflammatory, pro-survival, and tumorigenic activities...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28420988/heme-as-a-target-for-therapeutic-interventions
#12
REVIEW
Stephan Immenschuh, Vijith Vijayan, Sabina Janciauskiene, Faikah Gueler
Heme is a complex of iron and the tetrapyrrole protoporphyrin IX with essential functions in aerobic organisms. Heme is the prosthetic group of hemoproteins such as hemoglobin and myoglobin, which are crucial for reversible oxygen binding and transport. By contrast, high levels of free heme, which may occur in various pathophysiological conditions, are toxic via pro-oxidant, pro-inflammatory and cytotoxic effects. The toxicity of heme plays a major role for the pathogenesis of prototypical hemolytic disorders including sickle cell disease and malaria...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28418677/ph-dependence-of-ferricytochrome-c-conformational-transitions-during-binding-to-cardiolipin-membranes-evidence-for-histidine-as-the-distal-ligand-at-neutral-ph
#13
Bridget Milorey, Dmitry Malyshka, Reinhard Schweitzer-Stenner
The conformational changes of ferricytochrome c upon binding to cardiolipin-containing small unilamellar vesicles were studied at slightly acidic pH using fluorescence, visible circular dichroism, UV-visible absorption, and resonance Raman spectroscopy. The obtained spectroscopic response data suggest a mode of interaction, which is clearly distinct from the binding process observed at neutral pH. Evidence of a reversible and electrostatic binding mechanism under these conditions is provided through binding inhibition in the presence of 150 mM NaCl...
April 24, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28417080/applying-a-systems-approach-to-thyroid-physiology-looking-at-the-whole-with-a-mitochondrial-perspective-instead-of-judging-single-tsh-values-or-why-we-should-know-more-about-mitochondria-to-understand-metabolism
#14
REVIEW
Roy Moncayo, Helga Moncayo
Classical thinking in endocrine physiology squeezes our diagnostic handling into a simple negative feedback mechanism with a controller and a controlled variable. In the case of the thyroid this is reduced to TSH and fT3 and fT4, respectively. The setting of this tight notion has no free space for any additions. In this paper we want to challenge this model of limited application by proposing a construct based on a systems approach departing from two basic considerations. In first place since the majority of cases of thyroid disease develop and appear during life it has to be considered as an acquired condition...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28412459/no-changes-in-heme-synthesis-in-human-friedreich%C3%A2-s-ataxia-erythroid-progenitor-cells
#15
Hannes Steinkellner, Himanshu Narayan Singh, Martina U Muckenthaler, Hans Goldenberg, Rajeswari R Moganty, Barbara Scheiber-Mojdehkar, Brigitte Sturm
Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the protein frataxin. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid progenitor stem cells obtained from FRDA patients and healthy donors to investigate the putative role, if any, of frataxin deficiency in heme synthesis. We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA quantification. We used atomic absorption spectrophotometry for iron levels and a photometric assay for hemoglobin levels...
April 12, 2017: Gene
https://www.readbyqxmd.com/read/28412361/structural-insights-into-the-binding-mechanism-of-ido1-with-hydroxylamidine-based-inhibitor-incb14943
#16
You Wu, Tingting Xu, Jinsong Liu, Ke Ding, Jinxin Xu
IDO1 (indoleamine 2, 3-dioxygenase 1), a well characterized immunosuppressive enzyme, has attracted growing attention as a potential target for cancer immunotherapy. Hydroxylamidine compounds INCB024360 and INCB14943 (INCB024360 analogue) are highly effective IDO1 inhibitors. INCB024360 is undergoing clinical trials for treatment of various types of human cancer. Here, we determined the co-crystal structure of IDO1 and INCB14943, and elucidate the detailed binding mode. INCB14943 binds to heme iron in IDO1 protein through the oxime nitrogen...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28411639/nanoarmoring-of-enzymes-by-polymer-functionalized-iron-oxide-nanoparticles
#17
Gayan Premaratne, Leslie Coats, Sadagopan Krishnan
Polymer-armored enzymes loaded onto magnetic nanoparticles, as efficient nanobioreactors with enhanced properties, are described in this chapter. Polymers are useful macromolecules carrying a large number of surface charges and repeating units of desired chemical functional groups for linking enzymes onto them. Magnetic micro/nanoparticles have been widely used as enzyme carriers with the incorporation of suitable polymer layers. Synthesized iron oxide magnetic nanoparticles have been used to immobilize a peroxide-catalyzing enzyme-like heme protein: myoglobin using covalent and noncovalent strategies...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28409923/the-catalase-activity-of-catalase-peroxidases-is-modulated-by-changes-in-the-pka-of-the-distal-histidine
#18
Miguel Machuqueiro, Bruno Victor, Jacek Switala, Jacylyn Villanueva, Carme Rovira, Ignacio Fita, Peter C Loewen
The unusual Met-Tyr-Trp adduct composed of cross-linked side chains along with an associated mobile Arg is essential for catalase activity in catalase-peroxidases. In addition, acidic residues in the entrance channel, in particular an Asp and a Glu ∼7 and ∼15 Å, respectively, from the heme, significantly enhance catalase activity. The mechanism by which these channel carboxylates influence catalase activity is the focus of this work. Seventeen new variants with fewer and additional acidic residues have been constructed and characterized structurally and for enzymatic activity, revealing that their effect on activity is roughly inversely proportional to their distance from the heme and adduct, suggesting that the electrostatic potential of the heme cavity may be affected...
April 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28401968/tight-binding-of-heme-to-staphylococcus-aureus-isdg-and-isdi-precludes-design-of-a-competitive-inhibitor
#19
Matthew A Conger, Deepika Pokhrel, Matthew D Liptak
The micromolar equilibrium constants for heme dissociation from IsdG and IsdI reported in the literature call into question whether these enzymes are actually members of the iron-regulated surface determinant system of Staphylococcus aureus, which harvests heme iron from a host during infection. In order to address this question, the heme dissociation constants for IsdG and IsdI were reevaluated using three approaches. The heme dissociation equilibrium constants were measured using a UV/Vis absorption-detected assay analyzed with an assumption-free model, and using a newly developed fluorescence-detected assay...
April 12, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28401633/functional-soil-metagenomics-elucidation-of-polycyclic-aromatic-hydrocarbon-degradation-potential-following-12-years-of-in-situ-bioremediation
#20
Márcia Duarte, Agnes Nielsen, Amélia Camarinha-Silva, Ramiro Vilchez-Vargas, Thomas Bruls, Melissa L Wos-Oxley, Ruy Jauregui, Dietmar H Pieper
A culture-independent function-based screening approach was used to assess the microbial aerobic catabolome for polycyclic aromatic hydrocarbons degradation of a soil subjected to 12 years of in situ bioremediation. A total of 422,750 fosmid clones were screened for key aromatic ring-cleavage activities using 2,3-dihydroxybiphenyl as substrate. Most of the genes encoding ring-cleavage enzymes on the 768 retrieved positive fosmids could not be identified using primer-based approaches and, thus, 205 fosmid inserts were sequenced...
April 12, 2017: Environmental Microbiology
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