DOCSLIB.ORG

Bivalency As a Principle for Proteasome Inhibition (Polyoxyethylene͞x-Ray Structures)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bivalency As a Principle for Proteasome Inhibition (Polyoxyethylene͞x-Ray Structures) Proc. Natl. Acad. Sci. USA Vol. 96, pp. 5418–5422, May 1999 Biochemistry Bivalency as a principle for proteasome inhibition (polyoxyethyleneyx-ray structures) GU¨NTHER LOIDL,MICHAEL GROLL,HANS-JU¨RGEN MUSIOL,ROBERT HUBER, AND LUIS MORODER* Max-Planck-Institut fu¨r Biochemie, 82152 Martinsried, Germany Contributed by Robert Huber, March 22, 1999 ABSTRACT The proteasome, a multicatalytic protease, is by sequence homology (8). As defined by the character of the known to degrade unfolded polypeptides with low specificity in P1cleavagesitesofchromogenicsubstrates,trypsin-like,chymo- substrate selection and cleavage pattern. This lack of well- trypsin-like, and post-glutamyl-peptide hydrolytic (PGPH) defined substrate specificities makes the design of peptide- activities are exhibited by the eukaryotic proteasome. These based highly selective inhibitors extremely difficult. However, specificities, however, are not reflected in the cleavage pattern the x-ray structure of the proteasome from Saccharomyces of protein substrates, which seem to be cleaved at almost every cerevisiae reveals a unique topography of the six active sites in position (9–12). the inner chamber of the protease, which lends itself to The crystal structure of the 20S proteasome from Saccha- strategies of specific multivalent inhibition. Structure-derived romyces cerevisiae revealed an overall assembly of the 28 active site separation distances were exploited for the design subunits, which are arranged as a stack of four heptameric a b b a of homo- and heterobivalent inhibitors based on peptide 1–7, 1–7, 19-79, 19-79 rings to form a cylindrical particle (13). aldehyde head groups and polyoxyethylene as spacer element. Only three of the seven different b-subunits of one ring, i.e., Polyoxyethylene was chosen as a flexible, linear, and protea- b1, b2 and b5, are autoprocessed with generation of the some-resistant polymer to mimic unfolded polypeptide chains N-terminal nucleophile, the Thr1 residue essential for activity. and thus to allow access to the proteolytic chamber. Spacer Mutational studies in yeast have shown that these three lengths were selected that satisfy the inter- and intra-ring b-subunits are responsible for the three major proteolytic distances for occupation of the active sites from the S subsites. activities of the eukaryotic proteasome against small chromo- X-ray analysis of the proteasomeybivalent inhibitor complexes genic substrates and a large protein (14–16), i.e., b1 for the confirmed independent recognition and binding of the inhib- PGPH, b2 for the trypsin-like, and b5 for the chymotrypsin- itory head groups. Their inhibitory potencies, which are by 2 like activity. orders of magnitude enhanced, compared with pegylated The S1 pockets of these subunits are the major specificity monovalent inhibitors, result from the bivalent binding. The determinants and are appropriately polar and sized to accom- principle of multivalency, ubiquitous in nature, has been modate acidic, basic, and apolar P1 side chains, respectively, successfully applied in the past to enhance affinity and avidity but also bind noncomplementary residues (13), consistent with of ligands in molecular recognition processes. The present the low specificity of the proteasome (15). Besides tryptase study confirms its utility also for inhibition of multicatalytic (17), the proteasome is the only oligomeric protease in eu- protease complexes. karyotes with a known and well-defined geometry in the display of the active sites. Its unique arrangement lends itself The proteasome is a multicatalytic protease complex that is as a target for specific multivalent inhibition. The principle of involved in intracellular protein turnover in all three kingdoms multivalency as a tool for enhancing affinity and avidity was of life. The proteasome is located in both the cytosol and the first established in the chelate chemistry (18, 19) and later nucleus and acts in the degradation of abnormal, misfolded, or discovered in nature as an universal principle that is ubiqui- improperly assembled proteins, in stress response, cell cycle tously exploited to enhance selectivity and avidity in molecular control, cell differentiation, metabolic adaptation, and cellular recognition processes (20, 21). immune response. It also is involved in many pathophysiolog- We previously have reported the structure-based design of ical processes like inflammation and cancer and constitutes a bifunctional inhibitors of the proteasome that led to maleoyl- promising target for drug design. In mammals the proteasomes b-Ala-Val-Arg-H as a highly specific inhibitor of the trypsin- also are responsible for the production of the bulk of antigenic like activity (22). In the present study an approach to protea- peptides, which are presented via MHC class I molecules on some inhibition is presented, where the unique arrangement of the cell surface to cytotoxic T lymphocytes. The antiviral six active sites in one enzyme particle is used for the design of cytokine INF-g induces transcription of three additional b bivalent inhibitors (Fig. 1). By linking the N termini of two subunits (LMP2, MECL-1, and LMP7), which can replace tripeptide aldehydes as binding heads with a polymeric spacer their constitutive homologs (b1, b2, and b5) in newly assem- that is appropriate for simultaneous binding at two different bled proteasomes. The resulting immuno-proteasomes show active sites from the nonprimed subsites, bivalent inhibitors of altered cleavage patterns in vitro; these are thought to be up to 2 orders of magnitude enhanced binding affinities could essential for the proteasomal antigen processing (1). Most of be obtained. This principle of proteasome inhibition can be these functions are linked to an ubiquitin- and ATP-dependent applied to a wide range of monovalent proteasome inhibitors protein degradation pathway involving the 26S proteasome to benefit from the effects of multivalency on avidity and whose core and proteolytic chamber is formed by the 20S selectivity. proteasome (2–7). The eukaryotic 20S proteasome consists of a b seven different -type and seven different -type subunits, all Abbreviations: PEG, polyoxyethylene; AMC, 7-amido-4-methyl- of which have been cloned and sequenced and can be grouped coumarin; PGPH, post-glutamyl-peptide hydrolytic; DIEA, diisopro- pylethylamine; DMF, dimethylformamide; TBTU, 2-(1H-benzotria- The publication costs of this article were defrayed in part by page charge zole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate; Sc, semicar- bazone. payment. This article must therefore be hereby marked ‘‘advertisement’’ in *To whom reprint requests should be addressed at: Max-Planck- accordance with 18 U.S.C. §1734 solely to indicate this fact. Institut fu¨r Biochemie, Am Klopferspitz 18A, D-82152 Martinsried, PNAS is available online at www.pnas.org. Germany. e-mail: [email protected]. 5418 Downloaded by guest on September 27, 2021 Biochemistry: Loidl et al. Proc. Natl. Acad. Sci. USA 96 (1999) 5419 FIG. 1. Schematic representation of the central b-rings of the yeast proteasome with selected distances between active sites as derived from the x-ray structure (13). MATERIALS AND METHODS SCHEME 2. Synthesis of the PEGypeptide aldehyde conjugates. (a) 1 equ. H-Leu-Leu-Nle-Sc, TBTUy1-hydroxybenzotriazole (HOBt)y The polymeric spacer HOOC-(CH2)2-CO-NH-(PEG)19–25- DIEA, DMF. (b) 1 equ. H-Arg(Adoc)2-Val-Arg(Adoc)2-diethyl ac- NH-CO-(CH2)2-COOH was from Rapp Polymere (Tu¨bingen, etal, TBTUyHOBtyDIEA, DMF. (c) 2 equ. H-Leu-Leu-Nle-Sc, Germany), the substrates Z-Leu-Leu-Glu-b-naphthylamide, TBTUyHOBtyDIEA, DMF. (d) AcOH, 37% HCHO, MeOH. (e) 95% Bz-Phe-Val-Arg-7-amido-4-methyl-coumarin (AMC), and trifluoroacetic acid. Suc-Leu-Leu-Val-Tyr-AMC were purchased from Bachem, Proteasome Assay. A solution of proteasome from S. cer- and 20S proteasome from S. cerevisiae was prepared as de- z m scribed (13). evisiae in Tris HCl (pH 7.5; 450 l; 6.67 nM for PGPH, 5.56 nM Synthesis of the Inhibitors. The synthesis of Ac-Leu-Leu- for trypsin-like, and 1.11 nM for chymotrypsin-like activity) Nle-H (1) and H-Leu-Leu-Nle-semicarbazone (Sc) trifluoro- was incubated with the inhibitors at varying concentrations (1 nmol to 100 mmol) for1hat37°C. The fluorogenic substrates acetate (23) as well as H-Val-Arg(Adoc)2-diethyl acetal (22) for PGPH (Z-Leu-Leu-Glu-b-naphthylamide, 40 mM), tryp- have been reported. The tripeptide aldehyde Ac-Arg-Val- m Arg-H (2) was prepared as outlined in Scheme 1, and the sin-like (Bz-Phe-Val-Arg-AMC, 8 M), and chymotrypsin-like y assays (Suc-Leu-Leu-Val-Tyr-AMC, 8 mM) were dissolved in polyoxyethylene (PEG) peptide aldehyde conjugates (7-11) z were obtained following the synthetic routes of Scheme 2. the same Tris HCl buffer with a minimum amount of DMSO and added to the enzyme solution at 37°C to reach a final Stepwise N-terminal elongation of H-Leu-Leu-Nle-Sc with m y Boc-Gly-Pro-Gly-Gly-OH and (C H S) CH-CO-Leu-OH by volume of 500 l. Fluorescence excitation emission wave- 2 5 2 lengths were 360 nmy460 nm for AMC and 335 nmy410 nm for the benzotriazol-1-yl-oxytripyrrolidinephosphonium hexaflu- b orophosphate (24) and O-(7-azabenzotriazol-1-yl)-1,1,3,3- -naphthylamide. The rates of hydrolysis were monitored by tetramethyluronium hexafluorophosphate procedure (25), re- the fluorescence increase, and the initial linear portions of the spectively, and intermediate Na-Boc cleavage with 25% trif- curves (100–300 sec) were used to calculate the IC50 values. X-Ray Structure Analysis. Crystals of 20S proteasomes luoroacetic acid (TFA) in CH2Cl2 followed by the final y from S. cereisiae were grown in hanging drops at 24°C as aldehyde deprotection with Tl(NO3)3 in acetonitrile H2O led to the octapeptide 3. The propeptide-derived inhibitors 4-6 described (13). The crystals were soaked at final inhibitor were synthesized on solid support via side-chain attachment of concentrations of 5 mM for 12 h in a cryoprotecting buffer and Fmoc-Glu(OH)-Sc (where Fmoc 5 fluorenylmethoxycar- frozen in a stream of cold nitrogen gas (Oxford Cryo Systems, Oxford, U.K.).
Load more

Recommended publications
  • Date: To: September 22, 1 997 Mr Ian Johnston©
    22-SEP-1997 16:36 NOBELSTIFTELSEN 4& 8 6603847 SID 01 NOBELSTIFTELSEN The Nobel Foundation TELEFAX Date: September 22, 1 997 To: Mr Ian Johnston© Company: Executive Office of the Secretary-General Fax no: 0091-2129633511 From: The Nobel Foundation Total number of pages: olO MESSAGE DearMrJohnstone, With reference to your fax and to our telephone conversation, I am enclosing the address list of all Nobel Prize laureates. Yours sincerely, Ingr BergstrSm Mailing address: Bos StU S-102 45 Stockholm. Sweden Strat itddrtSMi Suircfatan 14 Teleptelrtts: (-MB S) 663 » 20 Fsuc (*-«>!) «W Jg 47 22-SEP-1997 16:36 NOBELSTIFTELSEN 46 B S603847 SID 02 22-SEP-1997 16:35 NOBELSTIFTELSEN 46 8 6603847 SID 03 Professor Willis E, Lamb Jr Prof. Aleksandre M. Prokhorov Dr. Leo EsaJki 848 North Norris Avenue Russian Academy of Sciences University of Tsukuba TUCSON, AZ 857 19 Leninskii Prospect 14 Tsukuba USA MSOCOWV71 Ibaraki Ru s s I a 305 Japan 59* c>io Dr. Tsung Dao Lee Professor Hans A. Bethe Professor Antony Hewlsh Department of Physics Cornell University Cavendish Laboratory Columbia University ITHACA, NY 14853 University of Cambridge 538 West I20th Street USA CAMBRIDGE CB3 OHE NEW YORK, NY 10027 England USA S96 014 S ' Dr. Chen Ning Yang Professor Murray Gell-Mann ^ Professor Aage Bohr The Institute for Department of Physics Niels Bohr Institutet Theoretical Physics California Institute of Technology Blegdamsvej 17 State University of New York PASADENA, CA91125 DK-2100 KOPENHAMN 0 STONY BROOK, NY 11794 USA D anni ark USA 595 600 613 Professor Owen Chamberlain Professor Louis Neel ' Professor Ben Mottelson 6068 Margarldo Drive Membre de rinstitute Nordita OAKLAND, CA 946 IS 15 Rue Marcel-Allegot Blegdamsvej 17 USA F-92190 MEUDON-BELLEVUE DK-2100 KOPENHAMN 0 Frankrike D an m ar k 599 615 Professor Donald A.
    [Show full text]
  • Liste Der Nobelpreisträger
    Physiologie Wirtschafts- Jahr Physik Chemie oder Literatur Frieden wissenschaften Medizin Wilhelm Henry Dunant Jacobus H. Emil von Sully 1901 Conrad — van ’t Hoff Behring Prudhomme Röntgen Frédéric Passy Hendrik Antoon Theodor Élie Ducommun 1902 Emil Fischer Ronald Ross — Lorentz Mommsen Pieter Zeeman Albert Gobat Henri Becquerel Svante Niels Ryberg Bjørnstjerne 1903 William Randal Cremer — Pierre Curie Arrhenius Finsen Bjørnson Marie Curie Frédéric John William William Mistral 1904 Iwan Pawlow Institut de Droit international — Strutt Ramsay José Echegaray Adolf von Henryk 1905 Philipp Lenard Robert Koch Bertha von Suttner — Baeyer Sienkiewicz Camillo Golgi Joseph John Giosuè 1906 Henri Moissan Theodore Roosevelt — Thomson Santiago Carducci Ramón y Cajal Albert A. Alphonse Rudyard \Ernesto Teodoro Moneta 1907 Eduard Buchner — Michelson Laveran Kipling Louis Renault Ilja Gabriel Ernest Rudolf Klas Pontus Arnoldson 1908 Metschnikow — Lippmann Rutherford Eucken Paul Ehrlich Fredrik Bajer Theodor Auguste Beernaert Guglielmo Wilhelm Kocher Selma 1909 — Marconi Ostwald Ferdinand Lagerlöf Paul Henri d’Estournelles de Braun Constant Johannes Albrecht Ständiges Internationales 1910 Diderik van Otto Wallach Paul Heyse — Kossel Friedensbüro der Waals Allvar Maurice Tobias Asser 1911 Wilhelm Wien Marie Curie — Gullstrand Maeterlinck Alfred Fried Victor Grignard Gerhart 1912 Gustaf Dalén Alexis Carrel Elihu Root — Paul Sabatier Hauptmann Heike Charles Rabindranath 1913 Kamerlingh Alfred Werner Henri La Fontaine — Robert Richet Tagore Onnes Theodore
    [Show full text]
  • Prof Hartmut Michel Prof Stephen Smale Dr John Robin Warren
    In conjunction with the Global Young Scientists Summit@one-north (GYSS@one-north) 2014, NUS is hosting a panel discussion on “Science and Society”. We are privileged to have 3 eminent scientists on the panel and Prof Barry Halliwell, Deputy President (Research and Technology) will be the moderator for this panel discussion. Date Monday, 20 January 2014 Time 6:30pm (Light refreshments will be served from 6pm) Lecture Theatre 35 Level 1, MD6, Centre for Translational Medicine Venue National University of Singapore 14 Medical Drive Singapore 117599 3 Eminent scientists on the panel: Prof Hartmut Michel Prof Stephen Smale Dr John Robin Warren A biochemist by training, Prof Michel One of the best known American Dr Warren is an Australian pathologist received the 1988 Nobel Prize in mathematicians, Prof Smale was who is credited, together with Barry Chemistry for unravelling how a awarded the Fields Medal in 1966 for Marshall, with the 1979 re-discovery of membrane-bound protein active in his work on topology in higher the bacterium Helicobacter pylori, photosynthesis is built up. dimensions. which they proved is the cause of stomach ulcers. In 2005, he was awarded the Nobel Prize in Medicine. Refer to annex for the profiles of the eminent panelists and panel moderator. This panel discussion is open to the public and admission is free. Registration is requested at www.pdsns.eventbrite.sg for catering purposes. Sir Andre Geim Regius and Royal Society Research Professor The University of Manchester Nobel Prize in Physics (2010) -------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- Sir Andre Geim is the Regius and Royal Society Research Professor at the University of Manchester.
    [Show full text]
  • 64Th Lindau Nobel Laureate Meeting – Accomodation Grants for Eusja Members
    64TH LINDAU NOBEL LAUREATE MEETING – ACCOMODATION GRANTS FOR EUSJA MEMBERS The Lindau Nobel Laureate Meetings and the European Union of Science Journalists’ Associations EUSJA have agreed to support the participation of EUSJA member journalists in the 64th Lindau Nobel Laureate Meeting. The meeting – dedicated to the Nobel Prize discipline of Physiology/Medicine – will be held at Lindau, Germany, from 28 June to 4 July 2014. More than 30 Nobel Laureates have announced their participation. They will meet approximately 600 aspiring undergraduates, PhD students, and post-docs from about 80 countries. Numerous lectures, panels, discussion sessions, and master classes, as well as a diversified programme of fringe events will account for an inspiring week of exchange and networking. EUSJA member journalists interested in reporting about the meeting can now apply for accommodation grants covering a four-night’s stay at a hotel in Lindau (additional nights may be booked at one’s own expense). Conditions Employed science journalists as well as freelance science journalists are eligible to apply for the grants. All applicants shall clearly define their specific journalistic interest in the Lindau Nobel Laureate Meetings. Further, all applicants shall indicate their media affiliation or indicate for which media they intend to cover the meeting. Application Process Please send – via your national association – an email with your application (consisting of a short CV and a motivation statement indicating your specific journalistic interests) to Mrs Viola Egikova, Vice-President of EUSJA by 14 April 2014 (deadline). Viola Egikova, Vice-President of EUSJA Phone: +7 499 256 5122 Fax: +7 499 259 63 60 Email: [email protected] All applicants will receive an answer to their application as soon as the organisers will have made their selection.
    [Show full text]
  • ROBERT HUBER Max-Planck-Institut Für Biochemie, 8033 Martinsried
    A STRUCTURAL BASIS OF LIGHT ENERGY AND ELECTRON TRANSFER IN BIOLOGY Nobel Lecture, December 8, 1988 by ROBERT HUBER Max-Planck-Institut für Biochemie, 8033 Martinsried Dedicated to Christa ABBREVIATIONS PBS, phycobilisomes; light harvesting organelles peripheral to the thylakoid membrane in cyanobacteria, which carry out oxygenic photosynthesis and have photosystems I and II; PE, PEC, PC, APC, phycoerythrin, phycoerythrocyanin, phycocyanin, allo- phycocyanin; biliprotein components in PBS with covalently attached tetra- pyrrole (bilin) pigments; PS I, II; photosynthetic reaction centers in chloroplasts and cyanobacteria; EBP; retinol binding protein; BBP, bilin (biliverdin IX); binding protein in Pieris brassicae; A Rps. viridis, bacteriochlorophyll-b containing purple bacterium carrying out anoxygenic photosynthesis; RC, reaction centre; C, H, L, M; the four subunits of the reaction centre from Rps. viridis: the cytochrome c subunit (C), with 4 haems displaying two redox potentials is located on the periplasmic side of the membrane; the L- and M- subunits are integrated in the membrane and their polypeptide chains span the membrane with 5 each, labelled A, B, C, D, E; they bind the bacteriochlorophyll-b (BChl-b or BC), bacteriopheophytin-b (BPh-b or BP), 2+ menaquinone-9 (Q A), ubiquinone-9 (UQ,Q B) and Fe cofactors; the sub- scripts P, A, M, L indicate pair, accessory, M-, L-subunit association, respec- tively; the H-subunit is located on the cytoplasmic side and its N-terminal α− helical segment (H) spans the membrane; P680, P960; primary electron donors in PS II and the RC of Rps. viridis, respectively, indicating the long wavelength absorption maxima; electronically excited states of P and D A; LHC, light harvesting complexes; light harvesting protein pigment complexes in BChl-a,b containing bacteria; R.
    [Show full text]
  • Some Verses by Chemist/Poet Roald Hoffmann and His Foreword To
    Some Verses by Chnist/Poet Roald Hoffsmmn and His Foreword to Vohme 12 of Essays of an Information Scientist ?. Numbers 51-52 December 23-30, 1991 An Unusual State of Matter for John M. Thomas in the beach sandt of Kerala, The invisible searchlights abradedfiom the gneiss, of hell, gamma rays, in the stream sands of North Carolina jlash down the lattice. onejhk nronazite, (he solitary Alpha particles, crazed nuclear mineral. In its crystalline beginning debris, are thrust on megavolt there was ordet there was a lattice. missions of chance destruction. And the atoms-cerium, lanthanum, The remnant atom, transmuted, recoils, thon”um, yttrium, phosphate4anced freeing itse~fiom its lattice paint, round their prv&stined sites, cannonballs awry thtzmgh tethered by the massless springs a crowded darrcefloo~ of electrostatics There are no exits to run to. and by their neighbors’ bulk. In chm”ncot’lisions of disruption They vibrated, neighbors are knockedfiom their sites. and sang The crystal Swellsfiom once limpid in quantized harmony long-range, short-range order to absent listeners, to me. to yellow-brown amorphousness. Faults, But the enemy is within. defects, The radioactive thorium k vacancies, nervous nuclei explode dislocations, in the random thrum interstitiais, ofa hammer undejine the metamict state. 1 of no Norse god. I fist became familiar with Roald Choosing a title for a volume that covers Hoffmarm’s poetry when we discussed the such a wi~e variety of topics is a diftlcult sciencdpmtry connection several years exercise. Just as the title of a book of poems ago.z “An Unusual State of Matter” is the cannot fully refleet its content.
    [Show full text]
  • S-1100-0025-02-00025.Pdf
    THE SECRETARY-GENERAL 27 March 2002 Excellency, I write to thank you for your letter of 21 March 2002 conveying a statement signed by over 100 Nobel Laureates and the article from Science. I was most grateful to receive a copy of this important statement, and the interesting accompanying commentary. With my best regards, Yours sincerely, His Excellency Mr. Paul Heinbecker Permanent Representative of Canada to the United Nations New York 'Pernrait.imi One Dag Hammarskjold Plaza 885 Second Avenue, 14th Floor New York, N.Y. 10017 ,, March 21,2002 H.E. Mr. Kofi Annan Secretary General of EXECUTIVE UFFiCE The United Nations OF7HESECEEWSENERAI Room S-3800A United Nations Plaza New York, N.Y. 10017 Excellency, At the request of Mr.. JohnPglanyi, Canadian Nobel Laureate (Chemistry, 198^Tam hereby conveymg abatement signed by in excess of 100 of your Mow Nobel Laureates, thit^as publishedin early December. Also attached is an excerptfrorn Science magazine which discusses the assertion ofhe Laureates' statement that "the most profound danger to world peace m Ae coming years will stem not from the irrational acts of states or individuals, but from the legitimate demands of the world's dispossessed.1' Yours sincerely, Paul Heinbecker Ambassador and Permanent Representative NEWS OF THE WEEK NOBEL STATEMENT the world's dispossessed. ... If, then, we per- mit the devastating power of modern Laureates Plead for weaponry to spread through this combustible human landscape, we invite a conflagration Laws, Not War that can engulf both rich and poor." Healthy
    [Show full text]
  • Nobel Letter Attny Gen Garland 5-4-2021
    May 4, 2021 The Honorable Merrick Garland Attorney General of the United States U.S. Department of Justice 950 Pennsylvania Avenue, NW Washington, D.C. 20530 Via email: [email protected] Dear Attorney General Garland, We Nobel Prize laureates representing all disciplines are writing you now in support of the April 27 letter from Members of Congress requesting that you immediately order a high-level Department of Justice review of an unorthodox case involving human rights lawyer Steven Donziger and that the Department reassert main jurisdiction over the case and conduct a review of the baseless charges against him. Donziger has now been under pre-trial house arrest in Manhattan for over 600 days and counting while awaiting trial on a petty misdemeanor charge resulting from a discovery dispute in the case of the United States v. Donziger, U.S. District Court S.D.N.Y Case No. 19 Cr. 561 (LAP); 11 Civ. 691 (LAK). The current date of his contempt of court trial, which has changed several times over the 600+ days of his house arrest, is May 10 in the Southern District of New York. In November of 2020, 55 Nobel Laureates released a public statement in support of Steven Donziger and at that time called for his release from house arrest, dismissal of the charges against him, the cessation of judicial harassment of him and assurances that any further legal actions against him be assigned to a neutral and unbiased judge. We believed then, as we do now, that as the letter to you from Members of Congress says the harassment of Donziger “involves a shameful
    [Show full text]
  • Image-Brochure-LNLM-2020-LQ.Pdf
    NOBEL LAUREATES PARTICIPATING IN LINDAU EVENTS SINCE 1951 Peter Agre | George A. Akerlof | Kurt Alder | Zhores I. Alferov | Hannes Alfvén | Sidney Altman | Hiroshi Amano | Philip W. Anderson | Christian B. Anfinsen | Edward V. Appleton | Werner Arber | Frances H. Arnold | Robert J. Aumann | Julius Axelrod | Abhijit Banerjee | John Bardeen | Barry C. Barish | Françoise Barré-Sinoussi | Derek H. R. Barton | Nicolay G. Basov | George W. Beadle | J. Georg Bednorz | Georg von Békésy |Eric Betzig | Bruce A. Beutler | Gerd Binnig | J. Michael Bishop | James W. Black | Elizabeth H. Blackburn | Patrick M. S. Blackett | Günter Blobel | Konrad Bloch | Felix Bloch | Nicolaas Bloembergen | Baruch S. Blumberg | Niels Bohr | Max Born | Paul Boyer | William Lawrence Bragg | Willy Brandt | Walter H. Brattain | Bertram N. Brockhouse | Herbert C. Brown | James M. Buchanan Jr. | Frank Burnet | Adolf F. Butenandt | Melvin Calvin Thomas R. Cech | Martin Chalfie | Subrahmanyan Chandrasekhar | Pavel A. Cherenkov | Steven Chu | Aaron Ciechanover | Albert Claude | John Cockcroft | Claude Cohen- Tannoudji | Leon N. Cooper | Carl Cori | Allan M. Cormack | John Cornforth André F. Cournand | Francis Crick | James Cronin | Paul J. Crutzen | Robert F. Curl Jr. | Henrik Dam | Jean Dausset | Angus S. Deaton | Gérard Debreu | Petrus Debye | Hans G. Dehmelt | Johann Deisenhofer Peter A. Diamond | Paul A. M. Dirac | Peter C. Doherty | Gerhard Domagk | Esther Duflo | Renato Dulbecco | Christian de Duve John Eccles | Gerald M. Edelman | Manfred Eigen | Gertrude B. Elion | Robert F. Engle III | François Englert | Richard R. Ernst Gerhard Ertl | Leo Esaki | Ulf von Euler | Hans von Euler- Chelpin | Martin J. Evans | John B. Fenn | Bernard L. Feringa Albert Fert | Ernst O. Fischer | Edmond H. Fischer | Val Fitch | Paul J.
    [Show full text]
  • Programme 70Th Lindau Nobel Laureate Meeting 27 June - 2 July 2021
    70 Programme 70th Lindau Nobel Laureate Meeting 27 June - 2 July 2021 Sessions Speakers Access Background Scientific sessions, Nobel Laureates, Clear guidance Everything else social functions, young scientists, to all viewing there is to know partner events, invited experts, and participation for a successful networking breaks moderators options meeting 2 Welcome Two months ago, everything was well on course to celebrate And yet: this interdisciplinary our 70th anniversary with you, in Lindau. anniversary meeting will feature But with the safety and health of all our participants being the most rich and versatile programme ever. of paramount importance, we were left with only one choice: It will provide plenty of opportunity to educate, inspire, go online. connect – and to celebrate! Join us. 4 PARTICIPATING LAUREATES 4 PARTICIPATING LAUREATES 5 Henry A. Joachim Donna George P. Hartmut Michael M. Adam Hiroshi Kissinger Frank Strickland Smith Michel Rosbash Riess Amano Jeffrey A. Peter Richard R. James P. Randy W. Brian K. Barry C. Dean Agre Schrock Allison Schekman Kobilka Barish John L. Harvey J. Robert H. J. Michael Martin J. Hall Alter Grubbs Kosterlitz Evans F. Duncan David J. Ben L. Edmond H. Carlo Brian P. Kailash Elizabeth Haldane Gross Feringa Fischer Rubbia Schmidt Satyarthi Blackburn Robert B. Reinhard Aaron Walter Barry J. Harald Takaaki Laughlin Genzel Ciechanover Gilbert Marshall zur Hausen Kajita Christiane Serge Steven Françoise Didier Martin Nüsslein- Haroche Chu Barré-Sinoussi Queloz Chalfie Volhard Anthony J. Gregg L. Robert J. Saul Klaus William G. Leggett Semenza Lefkowitz Perlmutter von Klitzing Kaelin Jr. Stefan W. Thomas C. Emmanuelle Kurt Ada Konstantin S.
    [Show full text]
  • The 1988 Nobel Prize in Chemistry Goes to Johann Deisenhofer
    EUGENE GARFIELD INSTITUTE FOR SCIENTIFIC lNFORMATION~ 3501 MARK ETST PHILADELPHIA PA 19104 The 1988 Nobel Prize in Chemistry Goes to Joham Deisenhofer, Robert Huber, and Hartnmt Michel for Elucidating Photosynthetic Processes Number 22 Mav,. 29, 1989 The 1988 Nobel Prize in chemistry was awarded to Johann Deisenhofer, Robert Huber, and Hartmut Michel, for revealing the atomic structure of a membrane-bound protein that drives photosynthesis in a purple bacterium. After briefly recounting the work that led to the prize, this essay examines the laureates’ most-cited papers and the IS1° research fronts in which they appear. Photosynthesis, as most schoolchildren As Douglas C. Youvan, Massachusetts In- learn, is the process by which sunlight is stitute of Technology, Cambridge, and converted into chemical energy—a process Barry L. Marrs, E.I. du Pent de Nemours essentird to most life on earth. During the & Company, Inc., Wihnington, Delaware, 1980s researchers made significant progress point out, recent studies on photosynthesis in elucidating the structural and chemical have employed bacteria belonging to the features of photosynthesis. The 1988 Nobel genus Rhodopseubrwtas. Although rhodo- Prize in chemistry recognizes three West pseudomonad photosynthesis differs in cer- German scientists for their contributions to tain respects from that carried out by higher the understanding of photosynthetic pro- plants, it is generally similar; and these bac- cesses and protein structure at the atomic teria are well suited to the techniques of mo- level. The three are Joham Deiserthofer, lecular genetics. The interiors of the bacteria Howard Hughes Medical Institute, and De- are filled with photosynthetic membranes, partment of Biochemistry, University of which are small, hollow spheres (or stacks Texas southwestern Medical Center, Dallas, of membranes, depending on the species) Texas; Robert Huber, Max Pkrnck Institute made of lipid bilayers.
    [Show full text]
  • Programme 2017 (Chemistry)
    Programme 67th Lindau Nobel Laureate Meeting 25 – 30 June 2017 MEETING APP TABLE OF CONTENTS WANT TO STAY UP TO DATE? Download the Lindau Nobel Laureate Meetings App. Scientific Programme page 8 • Up to date programme info & details About the Meetings page 30 • Session abstracts and poster abstracts • Ask questions during panel Supporters page 36 discussions • Participate in polls and surveys Maps page 44 • Interactive maps • Connect to other participants Good to Know page 52 • Social media integration Download the app (“Lindau Nobel Laureate Meetings”) in Android or iTunes app stores. Within the app, use the passphrase “quasicrystals” to download the guide for the 67th Lindau Nobel Laureate Meeting. 2 3 WELCOME WELCOME The 67th Lindau Nobel Laureate Meeting takes place during a climate of in- Each year, we aim to give young scientists more opportunities to present tense debate in society and science. Radical ideologies and remerging sepa- their work. This year we are adding poster flashes, short presentations, to ratist or nationalist sentiments add to a growing sense of insecurity and established formats such as master classes and afternoon discussions. For isolation. Further uncertainty is created by the trend of post-factual state- the second year in a row the meeting app will allow up-to-date programme ments and science denial in public discourse. information and new exchange opportunities. In 1951, the vision of the founders Franz Karl Hein, Gustav Wilhelm Parade The Science Trail, a public exhibition project integrating science into the and Count Lennart Bernadotte was to reconnect German scientists to the in- Lindau city space, is a new addition to our outreach efforts as part of our ternational scientific community, to overcome the borders between nations “Mission Education”.
    [Show full text]