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The Proteasome: a Proteolytic Nanomachine of Cell Regulation and Waste Disposal
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1695 (2004) 19–31 http://www.elsevier.com/locate/bba Review The proteasome: a proteolytic nanomachine of cell regulation and waste disposal Dieter H. Wolf *, Wolfgang Hilt Institut fu¨r Biochemie, Universita¨t Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany Available online 26 October 2004 Abstract The final destination of the majority of proteins that have to be selectively degraded in eukaryotic cells is the proteasome, a highly sophisticated nanomachine essential for life. 26S proteasomes select target proteins via their modification with polyubiquitin chains or, in rare cases, by the recognition of specific motifs. They are made up of different subcomplexes, a 20S core proteasome harboring the proteolytic active sites hidden within its barrel-like structure and two 19S caps that execute regulatory functions. Similar complexes equipped with PA28 regulators instead of 19S caps are a variation of this theme specialized for the production of antigenic peptides required in immune response. Structure analysis as well as extensive biochemical and genetic studies of the 26S proteasome and the ubiquitin system led to a basic model of substrate recognition and degradation. Recent work raised new concepts. Additional factors involved in substrate acquisition and delivery to the proteasome have been discovered. Moreover, first insights in the tasks of individual subunits or subcomplexes of the 19S caps in substrate recognition and binding as well as release and recycling of polyubiquitin tags have been obtained. D 2004 Elsevier B.V. All rights reserved. -
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, -
IMPDH2: a New Gene Associated with Dominant Juvenile-Onset Dystonia-Tremor Disorder
www.nature.com/ejhg BRIEF COMMUNICATION OPEN IMPDH2: a new gene associated with dominant juvenile-onset dystonia-tremor disorder 1,8 1,8 2 3 1,4 2 5 Anna Kuukasjärvi , Juan✉ C. Landoni , Jyrki Kaukonen , Mika Juhakoski , Mari Auranen , Tommi Torkkeli , Vidya Velagapudi and Anu Suomalainen 1,6,7 © The Author(s) 2021 The aetiology of dystonia disorders is complex, and next-generation sequencing has become a useful tool in elucidating the variable genetic background of these diseases. Here we report a deleterious heterozygous truncating variant in the inosine monophosphate dehydrogenasegene(IMPDH2) by whole-exome sequencing, co-segregating with a dominantly inherited dystonia-tremor disease in a large Finnish family. We show that the defect results in degradation of the gene product, causing IMPDH2 deficiency in patient cells. IMPDH2 is the first and rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides, a dopamine synthetic pathway previously linked to childhood or adolescence-onset dystonia disorders. We report IMPDH2 as a new gene to the dystonia disease entity. The evidence underlines the important link between guanine metabolism, dopamine biosynthesis and dystonia. European Journal of Human Genetics; https://doi.org/10.1038/s41431-021-00939-1 INTRODUCTION The disease-onset was between 9 and 20 years of age. Table 1 Dystonias are rare movement disorders characterised by sustained or summarises the clinical presentations. intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures. Dystonia can manifest as an isolated Case report symptom or combined with e.g. parkinsonism or myoclonus [1]. While Patient II-6 is a 46-year-old woman. -
Nucleotide Sequence and Analysis of the 58.3 to 65.5-Kb Early Region of Bacteriophage T4
Volume 14 Number 21 1986 Nucleic Acids Research Nucleotide sequence and analysis of the 58.3 to 65.5-kb early region of bacteriophage T4 Kristoffer Valerie 13.4, John Stevens', Mark Lynch'5, Earl E.Henderson12 and Jon K.de Riel1 'Fels Research Institute, and 2Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA and 3Department of Biochemistry and Biotechnology, Royal Institute of Technology, S-100 44 Stockholm, Sweden Received 21 July 1986; Revised and Accepted 30 September 1986 ABSTRACT The complete 7.2-kb nucleotide sequence from the 58.3 to 65.5-kb early region of bacteriophage T4 has been determined by Maxam and Gilbert sequencing. Computer analysis revealed at least 20 open reading frames (ORFs) within this sequence. All major ORFs are transcribed from the left strand, suggesting that they are expressed early during infection. Among the ORFs, we have identified the pIIII, II, denV and tk genes. The ORFs are very tightly spaced, even over Lapping in some instances, and when ORF interspacing occurs, promoter-like sequences can be implicated. Several of the sequences preceding the ORFs, in particular those at ipIII, ipII, denV, and orf6l.9, can potentially form stable stem-loop structures. INTRODUCTION Recently, considerable progress has been made studying the bacteriophage T4 genome at the molecular level due to the development of T4 strains with unmod- ified DNA suitable for digestion with restriction endonucleases (1). Many T4 genes have since been cloned, sequenced, and their gene products overproduced in Escherichia coli (for review see ref. 2). A majority of the T4 genes studied so far have been essential and non-essential genes with well-characterized pheno- types. -
Protein Expression Profile of Gluconacetobacter Diazotrophicus PAL5, a Sugarcane Endophytic Plant Growth-Promoting Bacterium
Proteomics 2008, 8, 1631–1644 DOI 10.1002/pmic.200700912 1631 RESEARCH ARTICLE Protein expression profile of Gluconacetobacter diazotrophicus PAL5, a sugarcane endophytic plant growth-promoting bacterium Leticia M. S. Lery1, 2, Ana Coelho1, 3, Wanda M. A. von Kruger1, 2, Mayla S. M. Gonc¸alves1, 3, Marise F. Santos1, 4, Richard H. Valente1, 5, Eidy O. Santos1, 3, Surza L. G. Rocha1, 5, Jonas Perales1, 5, Gilberto B. Domont1, 4, Katia R. S. Teixeira1, 6 and Paulo M. Bisch1, 2 1 Rio de Janeiro Proteomics Network, Rio de Janeiro, Brazil 2 Unidade Multidisciplinar de Genômica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 3 Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 4 Laboratório de Química de Proteínas, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 5 Laboratório de Toxinologia, Departamento de Fisiologia e Farmacodinâmica- Instituto Oswaldo Cruz- Fundac¸ão Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil 6 Laboratório de Genética e Bioquímica, Embrapa Agrobiologia, Seropédica, Brazil This is the first broad proteomic description of Gluconacetobacter diazotrophicus, an endophytic Received: September 25, 2007 bacterium, responsible for the major fraction of the atmospheric nitrogen fixed in sugarcane in Revised: December 18, 2007 tropical regions. Proteomic coverage of G. diazotrophicus PAL5 was obtained by two independent Accepted: December 19, 2007 approaches: 2-DE followed by MALDI-TOF or TOF-TOF MS and 1-DE followed by chromatog- raphy in a C18 column online coupled to an ESI-Q-TOF or ESI-IT mass spectrometer. -
The Phylogenetic Extent of Metabolic Enzymes and Pathways José Manuel Peregrin-Alvarez, Sophia Tsoka, Christos A
Downloaded from genome.cshlp.org on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press Letter The Phylogenetic Extent of Metabolic Enzymes and Pathways José Manuel Peregrin-Alvarez, Sophia Tsoka, Christos A. Ouzounis1 Computational Genomics Group, The European Bioinformatics Institute, EMBL Cambridge Outstation, Cambridge CB10 1SD, UK The evolution of metabolic enzymes and pathways has been a subject of intense study for more than half a century. Yet, so far, previous studies have focused on a small number of enzyme families or biochemical pathways. Here, we examine the phylogenetic distribution of the full-known metabolic complement of Escherichia coli, using sequence comparison against taxa-specific databases. Half of the metabolic enzymes have homologs in all domains of life, representing families involved in some of the most fundamental cellular processes. We thus show for the first time and in a comprehensive way that metabolism is conserved at the enzyme level. In addition, our analysis suggests that despite the sequence conservation and the extensive phylogenetic distribution of metabolic enzymes, their groupings into biochemical pathways are much more variable than previously thought. One of the fundamental tenets in molecular biology was ex- reliable source of metabolic information. The EcoCyc data- pressed by Monod, in his famous phrase “What is true for base holds information about the full genome and all known Escherichia coli is true for the elephant” (Jacob 1988). For a metabolic pathways of Escherichia coli (Karp et al. 2000). Re- long time, this statement has inspired generations of molecu- cently, the database has been used to represent computational lar biologists, who have used Bacteria as model organisms to predictions of other organisms (Karp 2001). -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
WO 2013/180584 Al 5 December 2013 (05.12.2013) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/180584 Al 5 December 2013 (05.12.2013) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C12N 1/21 (2006.01) C12N 15/74 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, C12N 15/52 (2006.01) C12P 5/02 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, C12N 15/63 (2006.01) HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/NZ20 13/000095 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, (22) International Filing Date: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 4 June 2013 (04.06.2013) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 61/654,412 1 June 2012 (01 .06.2012) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (71) Applicant: LANZATECH NEW ZEALAND LIMITED MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, [NZ/NZ]; 24 Balfour Road, Parnell, Auckland, 1052 (NZ). -
Catalytic Properties and Inhibition of Proline-Specific Dipeptidyl Peptidases II, IV and VII
UC Berkeley UC Berkeley Previously Published Works Title Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII Permalink https://escholarship.org/uc/item/4nf146zf Journal Biochemical Journal, 371 ISSN 0264-6021 Authors Leiting, B Pryor, K D Wu, J K et al. Publication Date 2003-04-01 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Biochem. J. (2003) 371, 525–532 (Printed in Great Britain) 525 Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII Barbara LEITING*1, KellyAnn D. PRYOR*, Joseph K. WU*, Frank MARSILIO*, Reshma A. PATEL*, Charles S. CRAIK†, Jonathan A. ELLMAN‡, Richard T. CUMMINGS* and Nancy A. THORNBERRY* *Department of Metabolic Disorders, Merck Research Laboratories, Mail code RY50G-236, P.O. Box 2000, Rahway, NJ 07065, U.S.A., †Department of Pharmaceutical Chemistry, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0446, U.S.A., and ‡Department of Chemistry, University of California, Berkeley, CA 94720, U.S.A. There is currently intense interest in the emerging group of strates and inhibitors for these enzymes, a complete biochemical proline-specific dipeptidases, and their roles in the regulation profile of these enzymes was obtained. The pH profiles, substrate of biological processes. Dipeptidyl peptidase IV (DPP-IV) is specificities as determined by positional scanning, Michaelis– involved in glucose metabolism by contributing to the regulation Menten constants and inhibition profiles for DPP-VII and DPP- of glucagon family peptides and has emerged as a potential target II were shown to be virtually identical, strongly supporting the for the treatment of metabolic diseases. -
Serine Proteases with Altered Sensitivity to Activity-Modulating
(19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants. -
Electrophoretic Variation in Adenylate Kinase Ofneisseria
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 10535-10539, November 1995 Genetics Electrophoretic variation in adenylate kinase of Neisseria meningitidis is due to inter- and intraspecies recombination (natural transformation/linkage disequilibrium/mosaic genes/multilocus enzyme electrophoresis/nonclonal population structure) EDWARD FEIL, GILL CARPENTER, AND BRIAN G. SPRATT* Molecular Microbiology Group, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom Communicated by John Maynard Smith, University of Sussex, Falmer, Brighton, United Kingdom, August 7, 1995 ABSTRACT In prokaryotic and eukaryotic organisms, their growth cycles and the availability of this mechanism of the electrophoretic variation in housekeeping enzymes from genetic exchange appears to have a profound effect on their natural populations is assumed to have arisen by the accu- evolution and population biology (3, 13-17). mulation of stochastic predominantly neutral mutations. In Caugant et al. (18) carried out an extensive MLEE survey of the naturally transformable bacterium Neisseria meningitidis, meningococci, analyzing variation at 15 enzyme loci in 688 we show that variation in the electrophoretic mobility of isolates recovered predominantly from patients with invasive adenylate kinase is due to inter- and intraspecies recombina- disease. Although the results from this survey appeared to tion rather than mutation. The nucleotide sequences of the imply relatively high levels of linkage disequilibrium, it has adenylate kinase gene (adk) from isolates that express the been pointed out (3, 17) that artificially high levels of linkage predominant slow electrophoretic variant were rather uni- disequilibrium may result from sampling bias, in this case form, differing in sequence at an average of 1.1% of nucleotide through the disproportionately high frequency in the data set sites. -
Genetic Polymorphism of the Angiotensin-Converting Enzyme (ACE) in Asthmatic Patients
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector RESPIRATORY MEDICINE (1998) 92, 1305-1310 Original Articles Genetic polymorphism of the angiotensin-converting enzyme (ACE) in asthmatic patients H. TOMITA, S. SATO, R. MATSUDA, N. OGISU, T. MORI, T. NIIMI AND S. SHIMIZU 2nd Department of Intemal Medicine, Nagoya City University Medical School, Nagoya, Japan Angiotensin-converting enzyme (ACE) inactivates bradykinin, substance P and neurokinin A, which are believed to play important roles in the pathogenesis of asthma, especially in neurogenic inflammation. It has recently been shown that an insertion (1)ldeletion (D) polymorphism in the ACE gene accounts for variation in serum ACE levels. There are thus three genotypes (insertion homozygote, II; deletion homozygote, DD; heterozygotes, DI). The serum ACE level with the DD type is reported to be about double that of the II type and intermediate in the DI case. In the present study, we examined whether asthma is linked with this ACE gene polymorphism. Seventy-one patients with asthma (27 males and 44 females) and 142 sex- and age-matched healthy controls were determined for their genotype by the polymerase chain reaction (PCR) method. Twenty-five asthmatics demonstrated the II type (352%) 37 the DI type (52.1%), and nine the DD type (12.7%). There were no significant differences in the distributions of genotypes and serum ACE levels between healthy controls and patients. No significant differences were evident in serum IgE levels, age at onset, proportion of atopic type patients and severity of asthma among the three genotypes.