The Marvels of Biosynthesis: Tracking Nature's Pathways
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Crystal Structure of Uroporphyrinogen III Synthase from Pseudomonas Syringae Pv. Tomato DC3000
Biochemical and Biophysical Research Communications 408 (2011) 576–581 Contents lists available at ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc Crystal structure of uroporphyrinogen III synthase from Pseudomonas syringae pv. tomato DC3000 ⇑ Shuxia Peng a,b, Hongmei Zhang a, Yu Gao a, Xiaowei Pan a, Peng Cao a, Mei Li a, Wenrui Chang a, a National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, PR China b Graduate University of the Chinese Academy of Sciences, Beijing 100049, PR China article info abstract Article history: Uroporphyrinogen III synthase (U3S) is one of the key enzymes in the biosynthesis of tetrapyrrole com- Received 11 April 2011 pounds. It catalyzes the cyclization of the linear hydroxymethylbilane (HMB) to uroporphyrinogen III Available online 19 April 2011 (uro’gen III). We have determined the crystal structure of U3S from Pseudomonas syringae pv. tomato DC3000 (psU3S) at 2.5 Å resolution by the single wavelength anomalous dispersion (SAD) method. Each Keywords: psU3S molecule consists of two domains interlinked by a two-stranded antiparallel b-sheet. The confor- Uroporphyrinogen III synthase mation of psU3S is different from its homologous proteins because of the flexibility of the linker between Crystal structure the two domains, which might be related to this enzyme’s catalytic properties. Based on mutation and Mutation activity analysis, a key residue, Arg219, was found to be important for the catalytic activity of psU3S. Enzymatic activity Tetrapyrroles Mutation of Arg219 to Ala caused a decrease in enzymatic activity to about 25% that of the wild type enzyme. -
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University of Bath PHD The extraction and chemistry of the metabolites of Mimosa tenuiflora and Papaver somniferum Ninan, Aleyamma Award date: 1990 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 23. Sep. 2021 THE EXTRACTION AND CHEMISTRY OF THE METABOLITES OF MIMOSA TENUIFLORA AND PAP AVER SOMNIFERUM. submitted by ALEYAMMA NINAN for the degree of Doctor of Philosophy of the University of Bath 1990 Attention is drawn to the fact that the copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without prior consent of the author. -
Hyperbilirubinemia
Porphyrins Porphyrins (Porphins) are cyclic tetrapyrol compounds formed by the linkage )). of four pyrrole rings through methenyl bridges (( HC In the reduced porphyrins (Porphyrinogens) the linkage of four pyrrole rings (tetrapyrol) through methylene bridges (( CH2 )) The characteristic property of porphyrins is the formation of complexes with the metal ion bound to nitrogen atoms of the pyrrole rings. e.g. Heme (iron porphyrin). Proteins which contain heme ((hemoproteins)) are widely distributed e.g. Hemoglobin, Myoglobin, Cytochromes, Catalase & Tryptophan pyrrolase. Natural porphyrins have substituent side chains on the eight hydrogen atoms numbered on the pyrrole rings. These side chains are: CH 1-Methyl-group (M)… (( 3 )) 2-Acetate-group (A)… (( CH2COOH )) 3-Propionate-group (P)… (( CH2CH2COOH )) 4-Vinyl-group (V)… (( CH CH2 )) Porphyrins with asymmetric arrangement of the side chains are classified as type III porphyrins while those with symmetric arrangement of the side chains are classified as type I porphyrins. Only types I & III are present in nature & type III series is more important because it includes heme. 1 Heme Biosynthesis Heme biosynthesis occurs through the following steps: 1-The starting reaction is the condensation between succinyl-CoA ((derived from citric acid cycle in the mitochondria)) & glycine, this reaction is a rate limiting reaction in the hepatic heme synthesis, it occurs in the mitochondria & is catalyzed by ALA synthase (Aminolevulinate synthase) enzyme in the presence of pyridoxal phosphate as a cofactor. The product of this reaction is α-amino-β-ketoadipate which is rapidly decarboxylated to form δ-aminolevulinate (ALA). 2-In the cytoplasm condensation reaction between two molecules of ALA is catalyzed by ALA dehydratase enzyme to form two molecules of water & one 2 molecule of porphobilinogen (PBG) which is a precursor of pyrrole. -
“Biosynthesis of Morphine in Mammals”
“Biosynthesis of Morphine in Mammals” D i s s e r t a t i o n zur Erlangung des akademischen Grades Doctor rerum naturalium (Dr. rer. nat.) vorgelegt der Naturwissenschaftlichen Fakultät I Biowissenschaften der Martin-Luther-Universität Halle-Wittenberg von Frau Nadja Grobe geb. am 21.08.1981 in Querfurt Gutachter /in 1. 2. 3. Halle (Saale), Table of Contents I INTRODUCTION ........................................................................................................1 II MATERIAL & METHODS ........................................................................................ 10 1 Animal Tissue ....................................................................................................... 10 2 Chemicals and Enzymes ....................................................................................... 10 3 Bacteria and Vectors ............................................................................................ 10 4 Instruments ........................................................................................................... 11 5 Synthesis ................................................................................................................ 12 5.1 Preparation of DOPAL from Epinephrine (according to DUNCAN 1975) ................. 12 5.2 Synthesis of (R)-Norlaudanosoline*HBr ................................................................. 12 5.3 Synthesis of [7D]-Salutaridinol and [7D]-epi-Salutaridinol ..................................... 13 6 Application Experiments ..................................................................................... -
Porphyrins & Bile Pigments
Bio. 2. ASPU. Lectu.6. Prof. Dr. F. ALQuobaili Porphyrins & Bile Pigments • Biomedical Importance These topics are closely related, because heme is synthesized from porphyrins and iron, and the products of degradation of heme are the bile pigments and iron. Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma, due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. • Metalloporphyrins & Hemoproteins Are Important in Nature Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methyne (==HC—) bridges. A characteristic property of the porphyrins is the formation of complexes with metal ions bound to the nitrogen atom of the pyrrole rings. Examples are the iron porphyrins such as heme of hemoglobin and the magnesium‐containing porphyrin chlorophyll, the photosynthetic pigment of plants. • Natural Porphyrins Have Substituent Side Chains on the Porphin Nucleus The porphyrins found in nature are compounds in which various side chains are substituted for the eight hydrogen atoms numbered in the porphyrin nucleus. As a simple means of showing these substitutions, Fischer proposed a shorthand formula in which the methyne bridges are omitted and a porphyrin with this type of asymmetric substitution is classified as a type III porphyrin. -
1. Introduction
Introduction 1. Introduction 1.1. Alkaloids The term alkaloid is derived from Arabic word al-qali, the plant from which “soda” was first obtained (Kutchan, 1995). Alkaloids are a group of naturally occurring low-molecular weight nitrogenous compounds found in about 20% of plant species. The majority of alkaloids in plants are derived from the amino acids tyrosine, tryptophan and phenylalanine. They are often basic and contain nitrogen in a heterocyclic ring. The classification of alkaloids is based on their carbon-nitrogen skeletons; common alkaloid ring structures include the pyridines, pyrroles, indoles, pyrrolidines, isoquinolines and piperidines (Petterson et al., 1991; Bennett et al., 1994). In nature, plant alkaloids are mainly involved in plant defense against herbivores and pathogens. Many of these compounds have biological activity which makes them suitable for use as stimulants (nicotine, caffeine), pharmaceuticals (vinblastine), narcotics (cocaine, morphine) and poisons (tubocurarine). The discovery of morphine by the German pharmacist Friedrich W. Sertürner in 1806 began the field of plant alkaloid biochemistry. However, the structure of morphine was not determined until 1952 due to its stereochemical complexity. Major technical advances occurred in this field allowing for the elucidation of selected alkaloid biosynthetic pathways. Among these were the introduction of radiolabeled precursors in the 1950s and the establishment in the 1970s of plant cell suspension cultures as an abundant source of enzymes that could be isolated, purified and characterized. Finally, the introduction of molecular techniques has made possible the isolation of genes involved in alkaloid secondary pathways (Croteau et al., 2000; Facchini, 2001). 1.1.1. Benzylisoquinoline alkaloids Isoquinoline alkaloids represent a large and varied group of physiologically active natural products. -
Morphinone Reductase for the Preparation Of
Europäisches Patentamt *EP000649465B1* (19) European Patent Office Office européen des brevets (11) EP 0 649 465 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: C12N 9/02, C12P 17/18, of the grant of the patent: C12Q 1/32 24.07.2002 Bulletin 2002/30 (86) International application number: (21) Application number: 93913236.1 PCT/GB93/01129 (22) Date of filing: 28.05.1993 (87) International publication number: WO 94/00565 (06.01.1994 Gazette 1994/02) (54) MORPHINONE REDUCTASE FOR THE PREPARATION OF HYDROMORPHONE AND HYDROCODONE MORPHINONE REDUKTASE ZUR HERSTELLUNG VON HYDROMORPHONE UND HYDROCODONE MORPHINONE REDUCTASE DESTINEE A LA PREPARATION D’HYDROMORPHONE ET D’HYDROCODONE (84) Designated Contracting States: (74) Representative: Perry, Robert Edward AT BE CH DE DK ES FR GB IE IT LI NL PT SE GILL JENNINGS & EVERY Broadgate House (30) Priority: 25.06.1992 GB 9213524 7 Eldon Street London EC2M 7LH (GB) (43) Date of publication of application: 26.04.1995 Bulletin 1995/17 (56) References cited: WO-A-90/13634 (73) Proprietor: MACFARLAN SMITH LIMITED Edinburgh EH11 2QA (GB) • THE BIOCHEMICAL JOURNAL vol. 274, no. 3, 15 March 1991, pages 875 - 880 NEIL C. BRUCE ET (72) Inventors: AL. ’Microbial degradation of the morphine • HAILES, Anne, Maria 59 Lower Road alkaloids. Purification and characterization of Kent DA8 1AY (GB) morphine dehydrogenase from Pseudomonas • FRENCH, Christopher, Edward putida M10’ Palmerston North (NZ) • BRUCE, Neil, Charles Cambridge CB2 1ND (GB) Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. -
Light-Independent Nitrogen Assimilation in Plant Leaves: Nitrate Incorporation Into Glutamine, Glutamate, Aspartate, and Asparagine Traced by 15N
plants Review Light-Independent Nitrogen Assimilation in Plant Leaves: Nitrate Incorporation into Glutamine, Glutamate, Aspartate, and Asparagine Traced by 15N Tadakatsu Yoneyama 1,* and Akira Suzuki 2,* 1 Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan 2 Institut Jean-Pierre Bourgin, Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), UMR1318, RD10, F-78026 Versailles, France * Correspondence: [email protected] (T.Y.); [email protected] (A.S.) Received: 3 September 2020; Accepted: 29 September 2020; Published: 2 October 2020 Abstract: Although the nitrate assimilation into amino acids in photosynthetic leaf tissues is active under the light, the studies during 1950s and 1970s in the dark nitrate assimilation provided fragmental and variable activities, and the mechanism of reductant supply to nitrate assimilation in darkness remained unclear. 15N tracing experiments unraveled the assimilatory mechanism of nitrogen from nitrate into amino acids in the light and in darkness by the reactions of nitrate and nitrite reductases, glutamine synthetase, glutamate synthase, aspartate aminotransferase, and asparagine synthetase. Nitrogen assimilation in illuminated leaves and non-photosynthetic roots occurs either in the redundant way or in the specific manner regarding the isoforms of nitrogen assimilatory enzymes in their cellular compartments. The electron supplying systems necessary to the enzymatic reactions share in part a similar electron donor system at the expense of carbohydrates in both leaves and roots, but also distinct reducing systems regarding the reactions of Fd-nitrite reductase and Fd-glutamate synthase in the photosynthetic and non-photosynthetic organs. -
Magnesium-Protoporphyrin Chelatase of Rhodobacter
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 1941-1944, March 1995 Biochemistry Magnesium-protoporphyrin chelatase of Rhodobacter sphaeroides: Reconstitution of activity by combining the products of the bchH, -I, and -D genes expressed in Escherichia coli (protoporphyrin IX/tetrapyrrole/chlorophyll/bacteriochlorophyll/photosynthesis) LUCIEN C. D. GIBSON*, ROBERT D. WILLOWSt, C. GAMINI KANNANGARAt, DITER VON WETTSTEINt, AND C. NEIL HUNTER* *Krebs Institute for Biomolecular Research and Robert Hill Institute for Photosynthesis, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, United Kingdom; and tCarlsberg Laboratory, Department of Physiology, Gamle Carlsberg Vej 10, DK-2500 Copenhagen Valby, Denmark Contributed by Diter von Wettstein, November 14, 1994 ABSTRACT Magnesium-protoporphyrin chelatase lies at Escherichia coli and demonstrate that the extracts of the E. coli the branch point of the heme and (bacterio)chlorophyll bio- transformants can convert Mg-protoporphyrin IX to Mg- synthetic pathways. In this work, the photosynthetic bacte- protoporphyrin monomethyl ester (20, 21). Apart from posi- rium Rhodobacter sphaeroides has been used as a model system tively identifying bchM as the gene encoding the Mg- for the study of this reaction. The bchH and the bchI and -D protoporphyrin methyltransferase, this work opens up the genes from R. sphaeroides were expressed in Escherichia coli. possibility of extending this approach to other parts of the When cell-free extracts from strains expressing BchH, BchI, pathway. In this paper, we report the expression of the genes and BchD were combined, the mixture was able to catalyze the bchH, -I, and -D from R. sphaeroides in E. coli: extracts from insertion of Mg into protoporphyrin IX in an ATP-dependent these transformants, when combined in vitro, are highly active manner. -
Effect of Anticancer Agents on Codeinone-Induced Apoptosis in Human Cancer Cell Lines
ANTICANCER RESEARCH 25: 4037-4042 (2005) Effect of Anticancer Agents on Codeinone-induced Apoptosis in Human Cancer Cell Lines RISA TAKEUCHI1,2, HIROSHI HOSHIJIMA1,2, NORIKO ONUKI1,2, HIROSHI NAGASAKA1, SHAHEAD ALI CHOWDHURY3, MASAMI KAWASE4 and HIROSHI SAKAGAMI2 1Division of Anesthesiology, Department of Comprehensive Medical Sciences, 2Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, and 3MPL (Meikai Phamaco-Medical Laboratory), Meikai University School of Dentistry, Sakado, Saitama 350-0283; 4Faculty of Phamaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan Abstract. The possible apoptosis-inducing activity of Opioids have been given to patients with cancer pain, codeinone, an oxidative metabolite of codeine, without or according to the WHO ladder against pain (4). According with anticancer drugs, was investigated. Codeinone induced to reports of Ventafridda et al., pain occurs in more than internucleosomal DNA fragmentation in human 50% of cancer patients, and the administration of opioids promyelocytic leukemia cells (HL-60), but not in human manifests significantly higher therapeutic effects against squamous cell carcinoma cells (HSC-2). Codeinone dose- cancer pain, compared with non-narcotics (5, 6). Although dependently activated caspase-3 in both of these cells, but to opioids have been used for patients in clinical situations, the a much lesser extent than that attained by actinomycin D. anticancer action of opioids has not been well investigated. This property of codeinone was similar to what we have Both opioids and anticancer drugs have been simultaneously found previously in ·,‚-unsaturated ketones. Codeinone did given for pain in cancer patients. However, there has been not activate caspase-8 or caspase-9 in these cells. -
Metabolic Versatility of the Nitrite-Oxidizing Bacterium Nitrospira
bioRxiv preprint doi: https://doi.org/10.1101/2020.07.02.185504; this version posted July 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 Metabolic versatility of the nitrite-oxidizing bacterium Nitrospira 2 marina and its proteomic response to oxygen-limited conditions 3 Barbara Bayer1*, Mak A. Saito2, Matthew R. McIlvin2, Sebastian Lücker3, Dawn M. Moran2, 4 Thomas S. Lankiewicz1, Christopher L. Dupont4, and Alyson E. Santoro1* 5 6 1 Department of Ecology, Evolution and Marine Biology, University of California, Santa Barbara, 7 CA, USA 8 2 Marine Chemistry and Geochemistry Department, Woods Hole Oceanographic Institution, 9 Woods Hole, MA, USA 10 3 Department of Microbiology, IWWR, Radboud University, Nijmegen, The Netherlands 11 4 J. Craig Venter Institute, La Jolla, CA, USA 12 13 *Correspondence: 14 Barbara Bayer, Department of Ecology, Evolution and Marine Biology, University of California, 15 Santa Barbara, CA, USA. E-mail: [email protected] 16 Alyson E. Santoro, Department of Ecology, Evolution and Marine Biology, University of 17 California, Santa Barbara, CA, USA. E-mail: [email protected] 18 19 Running title: Genome and proteome of Nitrospira marina 20 21 Competing Interests: The authors declare that they have no conflict of interest. 22 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.02.185504; this version posted July 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae
Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae Daniel, Bastian; Wallner, Silvia; Steiner, Barbara; Oberdorfer, Gustav; Kumar, Prashant; van der Graaff, Eric; Roitsch, Thomas; Sensen, Christoph W; Gruber, Karl; Macheroux, Peter Published in: PLOS ONE DOI: 10.1371/journal.pone.0156892 Publication date: 2016 Document version Publisher's PDF, also known as Version of record Citation for published version (APA): Daniel, B., Wallner, S., Steiner, B., Oberdorfer, G., Kumar, P., van der Graaff, E., ... Macheroux, P. (2016). Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae. PLOS ONE, 11(6), e0156892. https://doi.org/10.1371/journal.pone.0156892 Download date: 08. Apr. 2020 RESEARCH ARTICLE Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae Bastian Daniel1, Silvia Wallner1, Barbara Steiner1, Gustav Oberdorfer2, Prashant Kumar2, Eric van der Graaff3, Thomas Roitsch3,4, Christoph W. Sensen5, Karl Gruber2, Peter Macheroux1* 1 Institute of Biochemistry, Graz University of Technology, Graz, Austria, 2 Institute of Molecular Biosciences, University of Graz, Graz, Austria, 3 Department of Plant and Environmental Sciences, a11111 University of Copenhagen, Copenhagen, Denmark, 4 Global Change Research Centre, Czech Globe AS CR, v.v.i., Drásov 470, Cz-664 24 Drásov, Czech Republic, 5 Institute of Molecular Biotechnology, Graz University of Technology, Graz, Austria * [email protected] OPEN ACCESS Abstract Citation: Daniel B, Wallner S, Steiner B, Oberdorfer Berberine bridge enzyme-like (BBE-like) proteins form a multigene family (pfam 08031), G, Kumar P, van der Graaff E, et al.