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https://www.readbyqxmd.com/read/28922349/cytochrome-p450-and-flavin-containing-monooxygenase-families-age-dependent-differences-in-expression-and-functional-activity
#1
Nicole R Zane, Yao Chen, Michael Zhuo Wang, Dhiren R Thakker
BACKGROUND: Age-dependent differences in pharmacokinetics exist for metabolically cleared medications. Differential contributions in the cytochrome P450 3A (CYP3A), CYP2C, and flavin-containing monooxygenases (FMO) families play an important role in the metabolic clearance of a large number of drugs administered to children. METHODS: Unlike previous semi-quantitative characterization of age-dependent changes in the expression of genes and proteins (Western Analysis), this study quantifies both gene and absolute protein expression in the same fetal, pediatric and adult hepatic tissue...
September 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28921992/a-mechanistic-understanding-of-the-synergistic-potential-of-azole-fungicides-in-the-aquatic-invertebrate-gammarus-pulex
#2
Andrea Rösch, Michele Gottardi, Caroline Vignet, Nina Cedergreen, Juliane Hollender
Azole fungicides are known inhibitors of the important enzyme class cytochrome P450 monooxygenases (CYPs), thereby influencing the detoxification of co-occurring substances via biotransformation. This synergism in mixtures containing an azole has mostly been studied by effect measurements, while the underlying mechanism has been less well investigated. In this study, six azole fungicides (cyproconazole, epoxiconazole, ketoconazole, prochloraz, propiconazole and tebuconazole) were selected to investigate their synergistic potential and their CYP inhibition strength in the aquatic invertebrate Gammarus pulex...
September 18, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28921911/update-of-antitubercular-prodrugs-in-a-molecular-perspective-mechanisms-of-action-bioactivation-pathways-and-associated-resistances
#3
Vania Bernardes Genisson, Julie Laborde, Céline Deraeve
The place of prodrugs in the current antitubercular therapeutic arsenal is preponderant, since two of the four first-line antitubercular agents, isoniazid (INH) and pyrazinamide (PZA), need to be activated by Mycobacterium tuberculosis before exerting their activity. In addition, six other prodrugs can be found in the second- and third-line therapeutic regimens, namely ethionamide (ETH), prothionamide (PTH), p-aminosalicylic acid (PAS), thiacetazone (TAC), isoxyl (ISO) and the recently approved delamanid. The emergence of mycobacterial strains resistant to one or several antitubercular agents is one of the main issues of the antitubercular therapy...
September 16, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28921805/cytochrome-p450-diversification-and-hostplant-utilization-patterns-in-specialist-and-generalist-moths-birth-death-and-adaptation
#4
Bernarda Calla, Katherine Noble, Reed M Johnson, Kimberly K O Walden, Mary A Schuler, Hugh M Robertson, May R Berenbaum
Across insect genomes, the size of the cytochrome P450 monooxygenase (CYP) gene superfamily varies widely. CYPome size variation has been attributed to reciprocal adaptive radiations in insect detoxification genes in response to plant biosynthetic gene radiations driven by coevolution between herbivores and their chemically defended hostplants. Alternatively, variation in CYPome size may be due to random "birth and death" processes, whereby exponential increase via gene duplications is limited by random decay via gene death or transition via divergence...
September 15, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28919928/the-yeast-geotrichum-candidum-encodes-functional-lytic-polysaccharide-monooxygenases
#5
Simon Ladevèze, Mireille Haon, Ana Villares, Bernard Cathala, Sacha Grisel, Isabelle Herpoël-Gimbert, Bernard Henrissat, Jean-Guy Berrin
BACKGROUND: Lytic polysaccharide monooxygenases (LPMOs) are a class of powerful oxidative enzymes that have revolutionized our understanding of lignocellulose degradation. Fungal LPMOs of the AA9 family target cellulose and hemicelluloses. AA9 LPMO-coding genes have been identified across a wide range of fungal saprotrophs (Ascomycotina, Basidiomycotina, etc.), but so far they have not been found in more basal lineages. Recent genome analysis of the yeast Geotrichum candidum (Saccharomycotina) revealed the presence of several LPMO genes, which belong to the AA9 family...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#6
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28916997/coupled-reactions-by-coupled-enzymes-alcohol-to-lactone-cascade-with-alcohol-dehydrogenase-cyclohexanone-monooxygenase-fusions
#7
Friso S Aalbers, Marco W Fraaije
The combination of redox enzymes for redox-neutral cascade reactions has received increasing appreciation. An example is the combination of an alcohol dehydrogenase (ADH) with a cyclohexanone monooxygenase (CHMO). The ADH can use NADP(+) to oxidize cyclohexanol to form cyclohexanone and NADPH. Both products are then used by CHMO to produce ε-caprolactone. In this study, these two redox-complementary enzymes were fused, to create a self-sufficient bifunctional enzyme that can convert alcohols to esters or lactones...
September 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28915417/lc-ms-ms-quantification-of-7%C3%AE-hydroxy-4-cholesten-3-one-c4-in-rat-and-monkey-plasma
#8
Lijuan Kang, Thomas M Connolly, Naidong Weng, Wenying Jian
7α-hydroxy-4-cholesten-3-one (C4) is an oxidative enzymatic product of cholesterol metabolism via cholesterol 7α-hydroxylase, an enzyme also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1). C4 is a stable intermediate in the rate limiting pathway of bile acid biosynthesis. Previous studies showed that plasma C4 levels correlated with CYP7A1 enzymatic activity and could serve as a biomarker for bile acid synthesis. Here we developed and qualified a simple and robust high-throughput method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to quantify C4 in rat and monkey plasma...
September 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28911774/use-of-isotopes-and-isotope-effects-for-investigations-of-diiron-oxygenase-mechanisms
#9
Rahul Banerjee, Anna J Komor, John D Lipscomb
Isotope effects of four broad and overlapping categories have been applied to the study of the mechanisms of chemical reaction and regulation of nonheme diiron cluster-containing oxygenases. The categories are: (a) mass properties that allow substrate-to-product conversions to be tracked, (b) atomic properties that allow specialized spectroscopies, (c) mass properties that impact primarily vibrational spectroscopies, and (d) bond dissociation energy shifts that permit dynamic isotope effect studies of many types...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28911744/identification-of-two-novel-p450-genes-and-their-responses-to-deltamethrin-in-the-cabbage-moth-mamestra-brassicae-linnaeus
#10
Xia Zhou, Xing Fan, Yanling Gao, Jing Yang, Jin Qian, Dong Fan
Cytochrome P450 monooxygenases, found in virtually all living organisms, play an important role in the metabolism of xenobiotics such as drugs, pesticides, and plant toxins. In this study, we identified two novel cytochrome P450 genes from the cabbage moth, Mamestra brassicae Linnaeus. They were named CYP4M51 and CYP6AB56 (GenBank Accession Nos.: KX008607 and JQ901385, respectively) by the P450 Nomenclature Committee. Real-time quantitative reverse transcription revealed that CYP4M51 and CYP6AB56 were highly expressed in the fat bodies and were differentially expressed at different larval developmental stages...
September 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28901950/detecting-drug-target-binding-in-cells-using-fluorescence-activated-cell-sorting-coupled-with-mass-spectrometry-analysis
#11
Kris Wilson, Scott P Webster, John Peter Iredale, Xiaozhong Zheng, Natalie Z M Homer, Nhan Pham, Manfred Auer, Damian James Mole
The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity - the Toxicity-Affinity-Permeability-Selectivity (TAPS) technique...
September 13, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28900766/diversity-and-distribution-of-cyp-gene-family-in-bactrian-camel
#12
Surong Hasi, Jirimutu Yao, Siriguleng Yu, Yanan Tian
Cytochrome P450 (CYP) enzymes belong to a superfamily of monooxygenases which are phase I enzymes responsible for the first pass metabolism of about 90% of drugs in animals. However, these enzymes are often polymorphic and metabolism of the same drug in different species or different individuals is influenced by genetic and non-genetic factors. Bactrian camels are capable of survival in harsh living environments, being able to consume diets that are often toxic to other mammals and can tolerate extreme water and food deprivation...
September 12, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28900033/high-resolution-structure-of-a-lytic-polysaccharide-monooxygenase-from-hypocrea-jecorina-reveals-a-predicted-linker-as-an-integral-part-of-the-catalytic-domain
#13
Henrik Hansson, Saeid Karkehabadi, Nils Mikkelsen, Nicholai R Douglas, Steve Kim, Anna Lam, Thijs Kaper, Brad Kelemen, Katlyn K Meier, Stephen M Jones, Edward I Solomon, Mats Sandgren
For decades, the enzymes of the fungus Hypocrea jecorina have served as a model system for the breakdown of cellulose. Three-dimensional structures for almost all H. jecorina cellulose-degrading enzymes are available, except for HjLPMO9A, belonging to the AA9 family of lytic polysaccharide monooxygenases (LPMOs). These enzymes enhance the hydrolytic activity of cellulases and are essential for cost-efficient conversion of lignocellulosic biomass. Here, using structural and spectroscopic analyses, we found that native HjLPMO9A contains a catalytic domain and a family-1 carbohydrate-binding module (CBM1) connected via a linker sequence...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28899945/bindings-of-no-co-and-o2-to-multi-functional-globin-type-dehaloperoxidase-follow-the-sliding-scale-rule
#14
Gang Wu, Jing Zhao, Stefan Franzen, Ah-Lim Tsai
Dehaloperoxidase-hemoglobin (DHP), a multifunctional globin protein, functions not only as an oxygen carrier as typical globins such as myoglobin, but also as a peroxidase, a mono- and di-oxygenase, peroxygenase, and an oxidase. Kinetics of DHP binding to NO, CO, and O2 were characterized for wild type DHP A and B and the H55D and H55V DHP A mutants. All three gaseous ligands bind to DHP significantly more weakly than sperm whale myoglobin (SWMb). Both CO and NO bind to DHP in a one-step process to form a stable six-coordinate complex...
September 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28892091/oxidative-cyclization-of-prodigiosin-by-an-alkylglycerol-monooxygenase-like-enzyme
#15
Tristan de Rond, Parker Stow, Ian Eigl, Rebecca E Johnson, Leanne Jade G Chan, Garima Goyal, Edward E K Baidoo, Nathan J Hillson, Christopher J Petzold, Richmond Sarpong, Jay D Keasling
Prodiginines, which are tripyrrole alkaloids displaying a wide array of bioactivities, occur as linear and cyclic congeners. Identification of an unclustered biosynthetic gene led to the discovery of the enzyme responsible for catalyzing the regiospecific C-H activation and cyclization of prodigiosin to cycloprodigiosin in Pseudoalteromonas rubra. This enzyme is related to alkylglycerol monooxygenase and unrelated to RedG, the Rieske oxygenase that produces cyclized prodiginines in Streptomyces, implying convergent evolution...
September 11, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28888693/n-terminus-determines-activity-and-specificity-of-styrene-monooxygenase-reductases
#16
Thomas Heine, Anika Scholtissek, Adrie H Westphal, Willem J H van Berkel, Dirk Tischler
Styrene monooxygenases (SMOs) are two-enzyme systems that catalyze the enantioselective epoxidation of styrene to (S)-styrene oxide. The FADH2 co-substrate of the epoxidase component (StyA) is supplied by an NADH-dependent flavin reductase (StyB). The genome of Rhodococcus opacus 1CP encodes two SMO systems. One system, which we define as E1-type, displays homology to the SMO from Pseudomonas taiwanensis VLB120. The other system, originally reported as a fused system (RoStyA2B), is defined as E2-type. Here we found that E1-type RoStyB is inhibited by FMN, while RoStyA2B is known to be active with FMN...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28887418/expression-of-chitinases-in-listeria-monocytogenes-is-influenced-by-lmo0327-that-encodes-an-internalin-like-protein
#17
Dafni Katerina Paspaliari, Vicky Gaedt Kastbjerg, Hanne Ingmer, Magdalena Popowska, Marianne Halberg Larsen
The chitinolytic system of Listeria monocytogenes thus far comprises two chitinases, ChiA and ChiB, and a lytic polysaccharide monooxygenase, Lmo2467. The role of the system in the bacterium appears to be pleiotropic, as besides mediating hydrolysis of chitin, the second most ubiquitous carbohydrate in nature, the chitinases have been deemed important for colonization of unicellular moulds, as well as mammalian hosts. In order to identify additional components of the chitinolytic system, we screened a transposon mutant library for mutants exhibiting impaired chitin hydrolysis...
September 8, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28884316/improving-extracellular-production-of-serratia-marcescens-lytic-polysaccharide-monooxygenase-cbp21-and-aeromonas-veronii-b565-chitinase-chi92-in-escherichia-coli-and-their-synergism
#18
Yalin Yang, Juan Li, Xuewei Liu, Xingliang Pan, Junxiu Hou, Chao Ran, Zhigang Zhou
Lytic polysaccharide monooxygenases (LPMOs) can oxidize recalcitrant polysaccharides and boost the conversion of the second most abundant polysaccharide chitin by chitinase. In this study, we aimed to achieve the efficient extracellular production of Serratia marcescens LPMO CBP21 and Aeromonas veronii B565 chitinase Chi92 by Escherichia coli. Twelve signal peptides reported with high secretion efficiency were screened to assess the extracellular production efficiency of CBP21 and Chi92, with glycine used as a medium supplement...
September 7, 2017: AMB Express
https://www.readbyqxmd.com/read/28878754/marine-microbial-gene-abundance-and-community-composition-in-response-to-ocean-acidification-and-elevated-temperature-in-two-contrasting-coastal-marine-sediments
#19
Ashleigh R Currie, Karen Tait, Helen Parry, Beatriz de Francisco-Mora, Natalie Hicks, A Mark Osborn, Steve Widdicombe, Henrik Stahl
Marine ecosystems are exposed to a range of human-induced climate stressors, in particular changing carbonate chemistry and elevated sea surface temperatures as a consequence of climate change. More research effort is needed to reduce uncertainties about the effects of global-scale warming and acidification for benthic microbial communities, which drive sedimentary biogeochemical cycles. In this research, mesocosm experiments were set up using muddy and sandy coastal sediments to investigate the independent and interactive effects of elevated carbon dioxide concentrations (750 ppm CO2) and elevated temperature (ambient +4°C) on the abundance of taxonomic and functional microbial genes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28872846/tuning-the-diiron-core-geometry-in-carboxylate-bridged-macrocyclic-model-complexes-affects-their-redox-properties-and-supports-oxidation-chemistry
#20
Fang Wang, Sabine Becker, Mikael A Minier, Andrei Loas, Megan N Jackson, Stephen J Lippard
We introduce a novel platform to mimic the coordination environment of carboxylate-bridged diiron proteins by tethering a small, dangling internal carboxylate, (CH2)nCOOH, to phenol-imine macrocyclic ligands (H3PIMICn). In the presence of an external bulky carboxylic acid (RCO2H), the ligands react with [Fe2(Mes)4] (Mes = 2,4,6-trimethylphenyl) to afford dinuclear [Fe2(PIMICn)(RCO2)(MeCN)] (n = 4-6) complexes. X-ray diffraction studies revealed structural similarities between these complexes and the reduced diiron active sites of proteins such as Class I ribonucleotide reductase (RNR) R2 and soluble methane monooxygenase hydroxylase...
September 5, 2017: Inorganic Chemistry
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