Discovery of High Affinity Receptors for Dityrosine Through Inverse Virtual Screening and Docking and Molecular Dynamics
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Bacteria Belonging to Pseudomonas Typographi Sp. Nov. from the Bark Beetle Ips Typographus Have Genomic Potential to Aid in the Host Ecology
insects Article Bacteria Belonging to Pseudomonas typographi sp. nov. from the Bark Beetle Ips typographus Have Genomic Potential to Aid in the Host Ecology Ezequiel Peral-Aranega 1,2 , Zaki Saati-Santamaría 1,2 , Miroslav Kolaˇrik 3,4, Raúl Rivas 1,2,5 and Paula García-Fraile 1,2,4,5,* 1 Microbiology and Genetics Department, University of Salamanca, 37007 Salamanca, Spain; [email protected] (E.P.-A.); [email protected] (Z.S.-S.); [email protected] (R.R.) 2 Spanish-Portuguese Institute for Agricultural Research (CIALE), 37185 Salamanca, Spain 3 Department of Botany, Faculty of Science, Charles University, Benátská 2, 128 01 Prague, Czech Republic; [email protected] 4 Laboratory of Fungal Genetics and Metabolism, Institute of Microbiology of the Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic 5 Associated Research Unit of Plant-Microorganism Interaction, University of Salamanca-IRNASA-CSIC, 37008 Salamanca, Spain * Correspondence: [email protected] Received: 4 July 2020; Accepted: 1 September 2020; Published: 3 September 2020 Simple Summary: European Bark Beetle (Ips typographus) is a pest that affects dead and weakened spruce trees. Under certain environmental conditions, it has massive outbreaks, resulting in attacks of healthy trees, becoming a forest pest. It has been proposed that the bark beetle’s microbiome plays a key role in the insect’s ecology, providing nutrients, inhibiting pathogens, and degrading tree defense compounds, among other probable traits. During a study of bacterial associates from I. typographus, we isolated three strains identified as Pseudomonas from different beetle life stages. In this work, we aimed to reveal the taxonomic status of these bacterial strains and to sequence and annotate their genomes to mine possible traits related to a role within the bark beetle holobiont. -
Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis. -
A Review on Agmatinase Inhibitors
www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 12 December 2020 | ISSN: 2320-2882 A review on Agmatinase inhibitors 1Sunnica Biswas, 2Mr. R. T. Lohiya, 3Dr. Milind Umekar *1&2 Department Of Pharmaceutical Chemistry Smt. Kishoriti Bhoyar College of Pharmacy, Kamptee, Dst. Nagpur, 441002 Abstract : Agmatine is the product of arginine decarboxylation and can be hydrolyzed by agmatinase to putrescine, the precursor for biosynthesis of higher polyamines, spermidine, and spermine. Besides being an intermediate in polyamine metabolism, recent findings indicate that agmatine may play important regulatory roles in mammals. Agmatine, 4-aminobutyl guanidine, has recently been found in various mammalian organs and is thought to act as a neurotransmitter or neuromodulatory agent. The present study is to do a review on agmatine and its synthesized analogues till now for agmatinase inhibitory action. Agmatinase is a binuclear manganese metalloenzyme and belongs to the ureohydrolase superfamily that includes arginase, formiminoglutamase, and proclavaminate amidinohydrolase. Compared with a wealth of structural information available for arginases, no three dimensional structure of agmatinase has been reported. Agmatinase is an enzyme which blocks the mammalian agmatine which is ultimately responsible for the agmatine degradation in the body. Agmatinase is an enzyme which regulates the half life of agmatine in the brain. Hence a selective inhibitor of brain agmatinase is required. Several derivatives of agmatine are synthesized previously for agmatinase inhibitory activity but none of them showed selective inhibition. PZC (Piperazinecarboxamidine) is a derivative of agmatine or guanidine is expected to show selective inhibition of human agmatinase. A detailed review is carried out in order to understand the agmatinase inhibitor. -
Causes and Evaluation of Mildly Elevated Liver Transaminase Levels ROBERT C
Causes and Evaluation of Mildly Elevated Liver Transaminase Levels ROBERT C. OH, LTC, MC, USA, and THOMAS R. HUSTEAD, LTC, MC, USA Tripler Army Medical Center Family Medicine Residency Program, Honolulu, Hawaii Mild elevations in levels of the liver enzymes alanine transaminase and aspartate transaminase are commonly dis- covered in asymptomatic patients in primary care. Evidence to guide the diagnostic workup is limited. If the history and physical examination do not suggest a cause, a stepwise evaluation should be initiated based on the prevalence of diseases that cause mild elevations in transaminase levels. The most common cause is nonalcoholic fatty liver disease, which can affect up to 30 percent of the population. Other common causes include alcoholic liver disease, medication- associated liver injury, viral hepatitis (hepatitis B and C), and hemochromatosis. Less common causes include α1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic conditions (e.g., thyroid disorders, celiac disease, hemolysis, muscle disorders) can also cause elevated liver transaminase levels. Initial testing should include a fasting lipid profile; measurement of glucose, serum iron, and ferritin; total iron-binding capacity; and hepa- titis B surface antigen and hepatitis C virus antibody testing. If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate. Additional testing may include ultrasonog- raphy; measurement of α1-antitrypsin and ceruloplasmin; serum protein electrophoresis; and antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing. Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more. -
Purification Andsomeproperties of Cytosine Deaminase from Bakers
Agric. Biol. Chem., 53 (5), 1313-1319, 1989 1313 Purification and SomeProperties of Cytosine Deaminase from Bakers' Yeast Tohoru Katsuragi, Toshihiro Sonoda, Kin'ya Matsumoto, Takuo Sakai and Kenzo Tonomura Laboratory of Fermentation Chemistry, College of Agriculture, University of Osaka Prefecture, Sakai-shi, Osaka 591, Japan Received November 24, 1988 Cytosine deaminase (EC 3.5.4.1) was extracted from commercial compressed bakers' yeast and purified to an almost homogeneous state. The enzyme activity was more than 200U/mg of protein, which was several times higher than reported before. The molecular weight was 41,000 by gel permeation. The pi was at pH4.7. 5-Fluorocytosine, 5-methylcytosine, and creatinine were other substrates for the enzyme.An experiment with inhibitors suggested that the enzyme was an SH- enzyme. The enzyme was unstable to heat, with a half-life of about 0.5hr at 37°C. Characteristics of the enzyme, especially its substrate specificity, were compared with those reported earlier for other cytosine deaminases from bacteria and a mold. Local chemotherapy of cancer with the com- (5MC), a 5-substituted cytosine.4) 5FC, an- bined use of 5-fluorocytosine (5FC) given oral- other 5-substituted cytosine, is deaminated to ly and a cytosine deaminase capsule implant- 5FU in Saccharomyces cerevisiae.5) So, cy- ed locally may be possible.1} However, al- tosine deaminase of bakers' yeast should con- though this approach is successful in animal vert 5FCto 5FU, and could be used in place of experiments,1'2) there are problems when we E. coli cytosine deaminase. Although the yeast use the enzyme from Escherichia coli,3) which enzyme is unstable to heat (at 37.5°C),4) which is thermostable,1'3) and which can deaminate would prevent its use in long-term therapy in 5FC to 5-fluorouracil (5FU).1>3) First, it is the body, it might be stabilized by immobili- difficult to culture the bacteria on a large scale zation or other techniques. -
Molecular Basis of NDT-Mediated Activation of Nucleoside-Based Prodrugs and Application in Suicide Gene Therapy
biomolecules Article Molecular Basis of NDT-Mediated Activation of Nucleoside-Based Prodrugs and Application in Suicide Gene Therapy Javier Acosta 1,† , Elena Pérez 1,†, Pedro A. Sánchez-Murcia 2, Cristina Fillat 3,4 and Jesús Fernández-Lucas 2,5,* 1 Applied Biotechnology Group, European University of Madrid, c/ Tajo s/n, Villaviciosa de Odón, 28670 Madrid, Spain; [email protected] (J.A.); [email protected] (E.P.) 2 Division of Physiological Chemistry, Otto-Loewi Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/III, A-8010 Graz, Austria; [email protected] 3 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; cfi[email protected] 4 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 08036 Barcelona, Spain 5 Grupo de Investigación en Ciencias Naturales y Exactas, GICNEX, Universidad de la Costa, CUC, Calle 58 # 55-66 Barranquilla, Colombia * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Herein we report the first proof for the application of type II 20-deoxyribosyltransferase from Lactobacillus delbrueckii (LdNDT) in suicide gene therapy for cancer treatment. To this end, we first confirm the hydrolytic ability of LdNDT over the nucleoside-based prodrugs 20-deoxy-5- fluorouridine (dFUrd), 20-deoxy-2-fluoroadenosine (dFAdo), and 20-deoxy-6-methylpurine riboside (d6MetPRib). Such activity was significantly increased (up to 30-fold) in the presence of an acceptor nucleobase. To shed light on the strong nucleobase dependence for enzymatic activity, different molecular dynamics simulations were carried out. Finally, as a proof of concept, we tested the LdNDT/dFAdo system in human cervical cancer (HeLa) cells. -
Enzymatic Encoding Methods for Efficient Synthesis Of
(19) TZZ__T (11) EP 1 957 644 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C12N 15/10 (2006.01) C12Q 1/68 (2006.01) 01.12.2010 Bulletin 2010/48 C40B 40/06 (2006.01) C40B 50/06 (2006.01) (21) Application number: 06818144.5 (86) International application number: PCT/DK2006/000685 (22) Date of filing: 01.12.2006 (87) International publication number: WO 2007/062664 (07.06.2007 Gazette 2007/23) (54) ENZYMATIC ENCODING METHODS FOR EFFICIENT SYNTHESIS OF LARGE LIBRARIES ENZYMVERMITTELNDE KODIERUNGSMETHODEN FÜR EINE EFFIZIENTE SYNTHESE VON GROSSEN BIBLIOTHEKEN PROCEDES DE CODAGE ENZYMATIQUE DESTINES A LA SYNTHESE EFFICACE DE BIBLIOTHEQUES IMPORTANTES (84) Designated Contracting States: • GOLDBECH, Anne AT BE BG CH CY CZ DE DK EE ES FI FR GB GR DK-2200 Copenhagen N (DK) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • DE LEON, Daen SK TR DK-2300 Copenhagen S (DK) Designated Extension States: • KALDOR, Ditte Kievsmose AL BA HR MK RS DK-2880 Bagsvaerd (DK) • SLØK, Frank Abilgaard (30) Priority: 01.12.2005 DK 200501704 DK-3450 Allerød (DK) 02.12.2005 US 741490 P • HUSEMOEN, Birgitte Nystrup DK-2500 Valby (DK) (43) Date of publication of application: • DOLBERG, Johannes 20.08.2008 Bulletin 2008/34 DK-1674 Copenhagen V (DK) • JENSEN, Kim Birkebæk (73) Proprietor: Nuevolution A/S DK-2610 Rødovre (DK) 2100 Copenhagen 0 (DK) • PETERSEN, Lene DK-2100 Copenhagen Ø (DK) (72) Inventors: • NØRREGAARD-MADSEN, Mads • FRANCH, Thomas DK-3460 Birkerød (DK) DK-3070 Snekkersten (DK) • GODSKESEN, -
Neuroleptic Malignant Syndrome: Another Medical Cause of Acute Abdomen T.C.N
Postgraduate Medical Journal (1989) 65, 653 - 655 Postgrad Med J: first published as 10.1136/pgmj.65.767.653 on 1 September 1989. Downloaded from Missed Diagnosis Neuroleptic malignant syndrome: another medical cause of acute abdomen T.C.N. Lo, M.R. Unwin and I.W. Dymock Department ofMedicine, Stepping Hill Hospital, Stockport, UK. Summary: We present a patient with neuroleptic malignant syndrome and intestinal pseudo- obstruction misdiagnosed as being secondary to septicaemia. The management of the patient is discussed with emphasis on the role of creatine kinase and liver function tests. Introduction Neuroleptic malignant syndrome (NMS) is an occas- (92% neutrophils), serum sodium 130 mmol/l, potas- ional but potentially lethal idiosyncratic complication sium 5.1 mmol/l, urea 8.8 mmol/l, creatinine 79 1tmol/ ofneuroleptic drugs.'"2 By February 1989 the Commit- 1, bilirubin 15 Amol/l, alanine transaminase 837 IU/i tee on Safety of Medicines had received reports of 99 (normal 7-45), aspartate transaminase 392 IU/l (nor- cases. (Committee on Safety of Medicines, personal mal 9-41), gamma glutamyl transferase 15 IU/I (nor- Protected by copyright. Communication). It is thought that the condition is mal <65), alkaline phosphatase 62 IU/I (normal underdiagnosed.34 We report on a case of NMS of 35-125). Serial electrocardiograms showed sinus which the presenting features and therapeutic comp- tachycardia with no acute change. Abdominal X-ray lications occurring during the course of the illness revealed marked gaseous distension ofsmall and large served to further our knowledge in this condition. bowels with multiple fluid levels seen on decubitus films. -
Agmatinase Sirna (H): Sc-60060
SANTA CRUZ BIOTECHNOLOGY, INC. Agmatinase siRNA (h): sc-60060 BACKGROUND STORAGE AND RESUSPENSION Agmatinase (also known as agmatine ureohydrolase) results from the decar- Store lyophilized siRNA duplex at -20° C with desiccant. Stable for at least boxylation of L-arginine by arginine decarboxylase to form a metabolic inter- one year from the date of shipment. Once resuspended, store at -20° C, mediate in the biosynthesis of putresine and higher polyamines (spermidine avoid contact with RNAses and repeated freeze thaw cycles. and spermine). Agmatinase has been shown to play a role in several important Resuspend lyophilized siRNA duplex in 330 µl of the RNAse-free water biochemical processes in humans, ranging from effects on the central nervous provided. Resuspension of the siRNA duplex in 330 µl of RNAse-free water system to cell proliferation in cancer and viral replication. Agmatinase cat- makes a 10 µM solution in a 10 µM Tris-HCl, pH 8.0, 20 mM NaCl, 1 mM alyzes the hydrolysis of agmatine to putresine and urea and is a major target EDTA buffered solution. for drug therapy. Human Agmatinase retains about 30% identity to bacterial agmatinases and less than 20% identity to mammalian arginases. Residues APPLICATIONS required for binding of Mn2+ at the active site in bacterial Agmatinase and other members of the arginase superfamily are fully conserved in human Agmatinase siRNA (h) is recommended for the inhibition of Agmatinase Agmatinase. Agmatinase mRNA is most abundant in human liver and kidney, expression in human cells. but is also expressed in several other tissues, including skeletal muscle and brain. -
Stereoselective Synthesis of a 4- -Glucoside of Valienamine and Its X
www.nature.com/scientificreports OPEN Stereoselective synthesis of a 4‑⍺‑glucoside of valienamine and its X‑ray structure in complex with Streptomyces coelicolor GlgE1‑V279S Anshupriya Si1,4, Thilina D. Jayasinghe2,4, Radhika Thanvi1, Sunayana Kapil3, Donald R. Ronning2* & Steven J. Sucheck1* Glycoside hydrolases (GH) are a large family of hydrolytic enzymes found in all domains of life. As such, they control a plethora of normal and pathogenic biological functions. Thus, understanding selective inhibition of GH enzymes at the atomic level can lead to the identifcation of new classes of therapeutics. In these studies, we identifed a 4‑⍺‑glucoside of valienamine (8) as an inhibitor of Streptomyces coelicolor (Sco) GlgE1‑V279S which belongs to the GH13 Carbohydrate Active EnZyme family. The results obtained from the dose–response experiments show that 8 at a concentration of 1000 µM reduced the enzyme activity of Sco GlgE1‑V279S by 65%. The synthetic route to 8 and a closely related 4‑⍺‑glucoside of validamine (7) was achieved starting from readily available D‑maltose. A key step in the synthesis was a chelation‑controlled addition of vinylmagnesium bromide to a maltose‑derived enone intermediate. X‑ray structures of both 7 and 8 in complex with Sco GlgE1‑ V279S were solved to resolutions of 1.75 and 1.83 Å, respectively. Structural analysis revealed the valienamine derivative 8 binds the enzyme in an E2 conformation for the cyclohexene fragment. Also, the cyclohexene fragment shows a new hydrogen‑bonding contact from the pseudo‑diaxial C(3)–OH to the catalytic nucleophile Asp 394 at the enzyme active site. -
35 Disorders of Purine and Pyrimidine Metabolism
35 Disorders of Purine and Pyrimidine Metabolism Georges van den Berghe, M.- Françoise Vincent, Sandrine Marie 35.1 Inborn Errors of Purine Metabolism – 435 35.1.1 Phosphoribosyl Pyrophosphate Synthetase Superactivity – 435 35.1.2 Adenylosuccinase Deficiency – 436 35.1.3 AICA-Ribosiduria – 437 35.1.4 Muscle AMP Deaminase Deficiency – 437 35.1.5 Adenosine Deaminase Deficiency – 438 35.1.6 Adenosine Deaminase Superactivity – 439 35.1.7 Purine Nucleoside Phosphorylase Deficiency – 440 35.1.8 Xanthine Oxidase Deficiency – 440 35.1.9 Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency – 441 35.1.10 Adenine Phosphoribosyltransferase Deficiency – 442 35.1.11 Deoxyguanosine Kinase Deficiency – 442 35.2 Inborn Errors of Pyrimidine Metabolism – 445 35.2.1 UMP Synthase Deficiency (Hereditary Orotic Aciduria) – 445 35.2.2 Dihydropyrimidine Dehydrogenase Deficiency – 445 35.2.3 Dihydropyrimidinase Deficiency – 446 35.2.4 Ureidopropionase Deficiency – 446 35.2.5 Pyrimidine 5’-Nucleotidase Deficiency – 446 35.2.6 Cytosolic 5’-Nucleotidase Superactivity – 447 35.2.7 Thymidine Phosphorylase Deficiency – 447 35.2.8 Thymidine Kinase Deficiency – 447 References – 447 434 Chapter 35 · Disorders of Purine and Pyrimidine Metabolism Purine Metabolism Purine nucleotides are essential cellular constituents 4 The catabolic pathway starts from GMP, IMP and which intervene in energy transfer, metabolic regula- AMP, and produces uric acid, a poorly soluble tion, and synthesis of DNA and RNA. Purine metabo- compound, which tends to crystallize once its lism can be divided into three pathways: plasma concentration surpasses 6.5–7 mg/dl (0.38– 4 The biosynthetic pathway, often termed de novo, 0.47 mmol/l). starts with the formation of phosphoribosyl pyro- 4 The salvage pathway utilizes the purine bases, gua- phosphate (PRPP) and leads to the synthesis of nine, hypoxanthine and adenine, which are pro- inosine monophosphate (IMP). -
Purine Metabolism in Cultured Endothelial Cells
PURINE METABOLISM IN MAN-III Biochemical, Immunological, and Cancer Research Edited by Aurelio Rapado Fundacion Jimenez Diaz Madrid, Spain R.W.E. Watts M.R.C. Clinical Research Centre Harrow, England and Chris H.M.M. De Bruyn Department of Human Genetics University of Nijmegen Faculty of Medicine Nijmegen, The Netherlands PLENUM PRESS · NEW YORK AND LONDON Contents of Part Β I. PURINE METABOLISM PATHWAYS AND REGULATION A. De Novo Synthesis; Precursors and Regulation De Novo Purine Synthesis in Cultured Human Fibroblasts 1 R.B. Gordon, L. Thompson, L.A. Johnson, and B.T. Emmerson Comparative Metabolism of a New Antileishmanial Agent, Allopurinol Riboside, in the Parasite and the Host Cell 7 D. J. Nelson, S.W. LaFon, G.B. Elion, J.J. Marr, and R.L. Berens Purine Metabolism in Rat Skeletal Muscle 13 E. R. Tully and T.G. Sheehan Alterations in Purine Metabolism in Cultured Fibroblasts with HGPRT Deficiency and with PRPPP Synthetase Superactivity 19 E. Zoref-Shani and 0. Sperling Purine Metabolism in Cultured Endothelial Cells 25 S. Nees, A.L. Gerbes, B. Willershausen-Zönnchen, and E. Gerlach Determinants of 5-Phosphoribosyl-l-Pyrophosphate (PRPP) Synthesis in Human Fibroblasts 31 K.0, Raivio, Ch. Lazar, H. Krumholz, and M.A. Becker Xanthine Oxidoreductase Inhibition by NADH as a Regulatory Factor of Purine Metabolism 35 M.M. Jezewska and Z.W. Kaminski vii viii CONTENTS OF PART Β Β. Nucleotide Metabolism Human Placental Adenosine Kinase: Purification and Characterization 41 CM. Andres, T.D. Palella, and I.H. Fox Long-Term Effects of Ribose on Adenine Nucleotide Metabolism in Isoproterenol-Stimulated Hearts .