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Groupleader: Heiner Schirmer
Heiner Schirmer
Protein networks that maintain redox homeostasis in malaria parasites and their hosts. Pathophysiology and drug therapy.
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Obituary
Professor Dr. R. Heiner Schirmer, ist am 20. September 2016 verstorben.
Heiner Schirmer studierte Medizin und Philosophie an den Universitäten Heidelberg und Basel. Von 1970 bis 1980 war er wissenschaftlicher Assistent am Max-Planck-Institut für medizinische Forschung in Heidelberg, wo er sich der strukturellen und pharmakologischen Untersuchungen nukleotidbindender Enzyme widmete. In dieser Zeit schrieb er zusammen mit Georg E. Schulz die „Principles of Protein Structures“, die 1979 veröffentlicht wurden. Diese Monographie erschien 1980 auch in japanischer und 1982 in russischer Sprache und prägte eine ganze Generation angehender Protein-Kristallographen. 1980 erhielt Heiner Schirmer den Ruf auf eine Professur für Biochemie an der Medizinischen Fakultät der Universität Heidelberg. Hier war er zuerst am Institut für Biochemie II und seit dessen Gründung im Jahre 1996 am BZH tätig. Seine Forschungsgebiete umfassten die Biochemie humanpathogener Parasiten, insbesondere von Plasmodien, den Erregern der Malaria. Von 1992 bis 1993 diente er als Dekan der Fakultät für Naturwissenschaftliche Medizin der Universität Heidelberg. Auch in der Lehre war Heiner Schirmer stark engagiert. Von 2002 bis 2007 war er Sachverständiger für Biochemie am Institut für Medizinische und Pharmazeutische Prüfungsfragen (IMPP) in Mainz. Sein Ziel war es, Medizinstudenten für die Biochemie zu begeistern. Insbesondere seine mitreißenden und Studenten als Akteure einbindenden Vorlesungen sind vielen späteren Ärzten in bleibender Erinnerung geblieben.
2002 erhielt Heiner Schirmer den „Dream Action Award“ des niederländischen Chemiekonzerns DSM für die Entwicklung und klinische Prüfung Methylenblau-basierter Medikamentenkombinationen gegen Malaria bei Kindern in Westafrika. Bis kurz vor seinem Tod war er regelmäßig am BZH und arbeitet als Gründungsmitglied am Aufbau des Centre de Recherche en Santé de Nouna in Burkina Faso mit.
Neben seinen wissenschaftlichen Verdiensten bleibt seine Empathie für andere Menschen unvergesslich. Mit jeder Art Problem konnten Kollegen, Mitarbeiter und deren Angehörige oder Studenten zu ihm kommen und erhielten jederzeit Rat. Die Menschen am BZH und viele andere, die Heiner Schirmer kennenlernen durften, vermissen ihn sehr!
Research
Epidemiological and experimental evidence suggest that malaria parasites are more susceptible to reactive oxygen species than their human host cells. Antioxidative defense and redox homeostasis of the parasite are based on the glutathione and the thioredoxin systems. These systems form a network which involves dithiol proteins like glutathione reductase, glutaredoxins, thioredoxin reductase, and thioredoxin. The key enzymes of this antioxidative network are sufficiently different when comparing the malarial parasite Plasmodium falciparum, the insect vector Anopheles gambiae, and the human patient so that the design of specific inhibitors is warranted. These inhibitors might become of interest as antimalarial and/or as insecticidal agents (collaboration with PD H. M. Müller, EMBL).
Future projects will concentrate on glutathione-dependant processes in P. falciparum-parasitized erythrocytes (collaboration with Professor Katja Becker in Giessen). As members of the Research Focus SFB 544 Control of infectious diseases, we shall further work on the introduction of BlueCQ, an affordable combination of chloroquine and methylene blue, as an antimalarial drug. Methylene blue is a specific inhibitor of P. falciparum glutathione reductase but has a number of desired and unwanted side effects which are related to its redox properties. This project – a collaborative effort with the Centre de Recherche en Santé de Nouna (CRNS in Burkina Faso) and Drs. Schiek and Zich (DSM, Linz) is supported by the DSM Dream Action Award 2002.
Thioredoxin system and selenium metabolism. Another research focus of our group are Dr. Gromer´s studies on the interactions between thioredoxin system and selenium metabolism in infectious diseases and malignancies.
CV
born in 1942, deceased 20.09.2016
Academic Training and Positions
1961 Abitur at the Altes Gymnasium in Bremen
1961 - 1966 Study of philosophy and medicine
in Heidelberg and Basel
1963 - 1964 MD student
at the Max-Planck-Institute for Medical Research
1966/67/70 Internship and residency
at hospitals in Heidelberg, Karlsruhe and Stuttgart
1968 - 1969 Postdoc with Professor Lafayette Noda,
Dartmouth Medical School, N.H.
1970 - 1980 Group leader at the Department of Biophysics,
Max-Planck-Institute for Medical Research
in Heidelberg
1975 Habilitation in Biochemistry
at Heidelberg University
since 1976 Bicentennial Lecturer in Boston and Philadelphia
since 1980 Professor at Heidelberg University
Publications
Insight into the selenoproteome of the malaria parasite Plasmodium falciparum. Antioxid Redox Signal. 17(4):534-43.
Röseler A, Prieto JH, Iozef R, Hecker B, Schirmer RH, Külzer S, Przyborski J, Rahlfs S, Becker K (2012)
Subcellular localization of adenylate kinases in Plasmodium falciparum. FEBS Lett. 586(19):3037-43.
Ma J, Rahlfs S, Jortzik E, Schirmer RH, Przyborski JM, Becker K (2012)
"Lest we forget you--methylene blue...". Neurobiol Aging. 32(12):2325.e7-16.
Schirmer RH, Adler H, Pickhardt M, Mandelkow E (2011)
Die Entstehung und Entwicklung des Biochemie-Zentrums. in Wissenschaftsatlas der Universität Heidelberg 1386 – 2011, pp. 222-224. BIBLIOTHECA PALATINA Verlag. Schafmeier, T., Franke-Schaub, M., Schirmer, R. H. and Brunner, M. (2011)
Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites. J Am Chem Soc. 133(30):11557-71. Müller T, Johann L, Jannack B, Brückner M, Lanfranchi DA, Bauer H, Sanchez C, Yardley V, Deregnaucourt C, Schrével J, Lanzer M, Schirmer RH, Davioud-Charvet E (2011)
The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue. Redox Rep. 16(4):154-65.
Kasozi DM, Gromer S, Adler H, Zocher K, Rahlfs S, Wittlin S, Fritz-Wolf K, Schirmer RH, Becker K (2011)
The reducing milieu of parasitized cells as a target of antimalarial agents: Methylene blue as an ethical drug In: Apicomplexan Parasites. Molecular Approaches toward Targeted Drug Development (Becker K ed), pp. 115-136, Wiley-VCH, Weinheim
Meissner P, Adler H, Kasozi D, Fritz-Wolf K, Schirmer RH. (2011)
Efficacy of methylene blue monotherapy in semi-immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso. Trop Med Int Health 15(6):713-7.
Bountogo M, Zoungrana A, Coulibaly B, Klose C, Mansmann U, Mockenhaupt FP, Burhenne J, Mikus G, Walter-Sack I, Schirmer RH, Sié A, Meissner P, Müller O (2010)
Molecular genetics evidence for the in vivo roles of the two major NADPH-dependent disulfide reductases in the malaria parasite. J Biol Chem. 285(48):37388-95.
Buchholz K, Putrianti ED, Rahlfs S, Schirmer RH, Becker K, Matuschewski K (2010)
Artemisinin resistance on the Thai-Cambodian border. Lancet. 374(9699):1419.
Müller O, Sié A, Meissner P, Schirmer RH, Kouyaté B (2009)
CA/C1 peptidases of the malaria parasites Plasmodium falciparum and P. berghei and their mammalian hosts--a bioinformatical analysis. Biol Chem. 390(11):1185-97.
Xiao K, Jehle F, Peters C, Reinheckel T, Schirmer RH, Dandekar T. (2009)
Inherited glutathione reductase deficiency and Plasmodium falciparum malaria--a case study. PLoS One. 4(10):e7303.
Gallo V, Schwarzer E, Rahlfs S, Schirmer RH, van Zwieten R, Roos D, Arese P, Becker K (2009)
Myristoylated adenylate kinase-2 of Plasmodium falciparum forms a heterodimer with myristoyltransferase. Mol Biochem Parasitol. 163(2):77-84.
Rahlfs S, Koncarevic S, Iozef R, Mailu BM, Savvides SN, Schirmer RH, Becker K. (2009)
NMR assignments of oxidised thioredoxin from Plasmodium falciparum. Biomol NMR Assign. 3(2):159-61.
Munte CE, Becker K, Schirmer RH, Kalbitzer HR (2009)
Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial. PLoS One. 4(5):e5318.
Coulibaly B, Zoungrana A, Mockenhaupt FP, Schirmer RH, Klose C, Mansmann U, Meissner PE, Müller O. (2009)
Book Review on KC Nicolaou and T Montagnon. Molecules that changed the world. J Lab Med 32:382-383.
Schirmer H. (2008)
Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products. Mol Biochem Parasitol. 160(1):65-9. Buchholz K, Comini MA, Wissenbach D, Schirmer RH, Krauth-Siegel RL, Gromer S. (2008)
Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite. PLoS ONE. 3(6):e2474.
Buchholz K, Rahlfs S, Schirmer RH, Becker K, Matuschewski K. (2008)
Disulfide reductases as drug targets: Methylene blue combination therapies for falciparum malaria in African children. (2008) Flavins and Flavoproteins 2008 (Frago S, Gómez-Moreno C, Medina M eds) Prensas Universitarias Zaragoza. 481-486.
Schirmer RH, Adler H, Zappe HA, Gromer S, Becker K, Coulibaly B, Meissner P (2008)
Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum. Antimicrob Agents Chemother. 52(1):183-91.
Buchholz K, Schirmer RH, Eubel JK, Akoachere MB, Dandekar T, Becker K, Gromer S. (2008)
Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS ONE. 3(2):e1630.
Zoungrana A, Coulibaly B, Sié A, Walter-Sack I, Mockenhaupt FP, Kouyaté B, Schirmer RH, Klose C, Mansmann U, Meissner P, Müller O. (2008)
Antioxidative Enzyme des Malariaerregers als Drug Targets. BIOspektrum 13:138-141.
Becker K, Schirmer RH. (2007)
Attitudes towards colouration effects associated with methylene blue malaria treatment in rural Burkina Faso. Curare 30:27-34.
Sanon M, Mandi G, De Allegri M, Schirmer H, Meissner P, Müller O. (2007)
Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum. Antimicrob Agents Chemother Epub.
Buchholz K, Schirmer RH, Eubel JK, Akoachère MB, Dandekar T, Becker K, Gromer S. (2007)
Kontrolle tropischer Infektionskrankheiten. Multidisziplinäre Forschungsprojekte in Burkina Faso. Flugmedizin, Tropenmedizin, Reisemedizin (FTR) 14: 31-32.
Müller O, Schirmer H. (2007)
Malaria ist kein Tabu mehr. Focus Campus 20:52-55.
Rosskopf K, Schirmer H. (2007)
Methylenblau in der Malariatherapie. Eine Alternative für Afrika? Flugmedizin, Tropenmedizin, Reisemedizin (FTR) 14: 33-35.
Müller O, Meissner P, Schirmer RH. (2007)
Molecular basis of glutathione reductase deficiency in human blood cells. Blood 109:3560-3566.
Kamerbeek NM, van Zwieten R, de Boer M, Morren G, Vuil H, Bannink N, Lincke C, Dolman KM, Becker K, Schirmer RH, Gromer S, Roos D. (2007)
A fluoro analogue of the menadione derivative 6-[2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme. J Am Chem Soc. 128(33):10784-94.
Bauer H, Fritz-Wolf K, Winzer A, Kühner S, Little S, Yardley V, Vezin H, Palfey B, Schirmer RH, Davioud-Charvet E. (2006)
Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrob Agents Chemother. 50(9):3132-41.
Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W, Elliott DA, Joiner KA, Schirmer RH, Anderson KS. (2006)
Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malar J. 5:84.
Meissner PE, Mandi G, Coulibaly B, Witte S, Tapsoba T, Mansmann U, Rengelshausen J, Schiek W, Jahn A, Walter-Sack I, Mikus G, Burhenne J, Riedel KD, Schirmer RH, Kouyaté B, Müller O. (2006)
Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein. Nucleic Acids Res. 34(14):4012-24.
Lobanov AV, Gromer S, Salinas G, Gladyshev VN. (2006)
The Plasmodium selenoproteome. Nucleic Acids Res. 34(2):496-505.
Lobanov AV, Delgado C, Rahlfs S, Novoselov SV, Kryukov GV, Gromer S, Hatfield DL, Becker K, Gladyshev VN. (2006)
(1)H, (13)C, and (15)N Sequence-specific Resonance Assignment and Secondary Structure of Plasmodium falciparum Thioredoxin. J Biomol NMR. 32(4):340.
Munte CE, Becker K, Schirmer RH, Kalbitzer HR. (2005)
Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts. Biol Chem. 386(1):41-52.
Akoachere M, Iozef R, Rahlfs S, Deponte M, Mannervik B, Creighton DJ, Schirmer H, Becker K. (2005)
Comparative structural analysis of oxidized and reduced thioredoxin from Drosophila melanogaster. J Mol Biol. 345(5):1119-30.
Wahl MC, Irmler A, Hecker B, Schirmer RH, Becker K. (2005)
Diagnosis of red cell G6PD deficiency in rural Burkina Faso. Comparison of a rapid fluorescent enzyme test on filter paper with polymerase chain reaction based genotyping. Br J Haematol. 131: 395-9.
Meissner PE, Coulibaly B, Mandi G, Mansmann U, Witte S, Schiek W, Müller O, Schirmer RH, Mockenhaupt FP, Bienzle U. (2005)
Die große Schande. Frank Rund Plus. 272: 23.
Schirmer RH. (2005)
Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. Angew Chem Int Ed. 44(5):690-715. Krauth-Siegel RL, Bauer H, Schirmer RH. (2005)
Dithiolproteine als Hüter des intrazellulären Redoxmilieus bei Parasiten: alte und neue Wirkstoff-Targets bei Trypanosomiasis und Malaria. Angew Chem. 117:698-724. Krauth-Siegel RL, Bauer H, Schirmer RH. (2005)
Effects of antioxidants on glutathione levels and clinical recovery from the malnutrition syndrome kwashiorkor - a pilot study. Redox Rep. 10(4):215-26.
Becker K, Pons-Kühnemann J, Fechner A, Funk M, Gromer S, Gross HJ, Grünert A, Schirmer RH. (2005)
Human selenoproteins at a glance. Cell Mol Life Sci. 62: 2414-37.
Gromer S, Eubel JK, Lee BL, Jacob J. (2005)
In Vitro Assessment of Methylene Blue on Chloroquine-Sensitive and -Resistant Plasmodium falciparum Strains Reveals Synergistic Action with Artemisinins. Antimicrob Agents Chemother. 49(11):4592-7.
Akoachere M, Buchholz K, Fischer E, Burhenne J, Haefeli WE, Schirmer RH, Becker K. (2005)
Large thioredoxin reductases – A fairy tail story. Flavins and Flavoproteins 2005 (Nishino T, Miura R, Tanokura M, Fukui K Ed) ArchiTect Inc Tokyo. 295-306.
Gromer S, Jacob J, Schirmer RH. (2005)
Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso. Trop Med Int Health. 10(1):32-8.
Mandi G, Witte S, Meissner P, Coulibaly B, Mansmann U, Rengelshausen J, Schiek W, Jahn A, Sanon M, Wüst K, Walter-Sack I, Mikus G, Burhenne J, Riedel KD, Schirmer H, Kouyate B, Müller O. (2005)
Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841]. Malar J. 4:45.
Meissner PE, Mandi G, Witte S, Coulibaly B, Mansmann U, Rengelshausen J, Schiek W, Jahn A, Sanon M, Tapsoba T, Walter-Sack I, Mikus G, Burhenne J, Riedel KD, Schirmer H, Kouyate B, Muller O. (2005)
Synthesis of 5-nitro-2-furancarbohydrazides and their cis-diamminedichloroplatinum complexes as bitopic and irreversible human thioredoxin reductase inhibitors. J Med Chem. 48(22):7024-39. Millet, R., Urig, S., Jacob, J., Amtmann, E., Moulinoux, J. P., Gromer, S., Becker, K., & Davioud-Charvet, E. (2005)
The conserved histidine 106 of large thioredoxin reductases is likely to have a structural role but not a base catalyst function. FEBS Lett. 579(3):745-8.
Jacob J, Schirmer RH, Gromer S. (2005)
YANA - a software tool for analyzing flux modes, gene-expression and enzyme activities. BMC Bioinformatics. 6(1):135.
Schwarz R, Musch P, von Kamp A, Engels B, Schirmer H, Schuster S, Dandekar T. (2005)
5-substituted tetrazoles as bioisosteres of carboxylic acids. Bioisosterism and mechanistic studies on glutathione reductase inhibitors as antimalarials. J Med Chem. 47(24):5972-83. Biot C, Bauer H, Schirmer RH, Davioud-Charvet E. (2004)
Adenylate kinase and GTP:AMP phosphotransferase of the malarial parasite Plasmodium falciparum. Central players in cellular energy metabolism. Mol Biochem Parasitol. 136(2):211-20.
Ulschmid JK, Rahlfs S, Schirmer RH, Becker K. (2004)
Biochemistry-based health care research. Methylene blue, malaria, methemoglobin, and malnutrition. Health Research in Developing Countries (Becher H, Kouyaté B eds). Springer Verlag, Berlin-Heidelberg. 285-297.
Coulibaly B, Eubel J, Gromer S, Schirmer RH. (2004)
Die Entdeckung der Nukleinsäure-Bausteine: ein Beitrag zum 150. Geburtstag Albrecht Kossels, Nobelpreisträger für Physiologie oder Medizin 1910. Klinische Chemie Mitteilungen. 35(3/4):46-54.
Steiner M, Schmidt H, Lindahl S, Kossel AH, Schuff-Werner P, Schirmer H. (2004)
Medikamente für die Armen - Die Biomedizin des 21. Jahrhunderts darf nicht nur für die Minderheit der Wohlhabenden forschen. Spektrum der Wissenschaft. 110-113.
Schirmer H. (2004)
Pharmacogenomic strategies against resistance development in microbial infections. Pharmacogenomics. 5(4):361-79.
Ziebuhr W, Xiao K, Coulibaly B, Schwarz R, Dandekar T. (2004)
The thioredoxin system - from science to clinic. Med Res Rev. 24(1):40-89.
Gromer S, Urig S, Becker K. (2004)
A putative glutathione peroxidase of Drosophila encodes a thioredoxin peroxidase that provides resistance against oxidative stress but fails to complement a lack of catalase activity. Biol Chem. 384:463-472.
Missirlis F, Rahlfs S, Dimopoulos N, Bauer H, Becker K, Hilliker A, Phillips JP, Jäckle H. (2003)
Active sites of thioredoxin reductases: Why selenoproteins? Proc Natl Acad Sci U S A. 100(22):12618-12623
Gromer S, Johannson L, Bauer H, Arscott LD, Rauch S, Ballou D, Williams CH Jr, Schirmer RH, Arnér ESJ. (2003)
Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development. J Mol Biol. 328(4):893-907.
Sarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, Karplus PA. (2003)
Glutathione-functions and metabolism in the malarial parasite Plasmodium falciparum. Biol Chem. 384(4):551-66.
Becker K, Rahlfs S, Nickel C, Schirmer RH. (2003)
Glyoxalase I of the malarial parasite Plasmodium falciparum. Evidence for subunit fusion. FEBS Lett. 554:284-288.
Iozef R, Rahlfs R, Chang T, Schirmer RH, Becker K. (2003)
Mechanism-based inactivation of thioredoxin reductase from Plasmodium falciparum by Mannich bases. Implications for cytotoxicity. Biochemistry 42(45):13319-13330. Davioud-Charvet E, McLeish MJ, Veine DM, Giegel D, Arscott LD, Andricopulo AD, Becker K, Müller S, Schirmer RH, Williams CH Jr, Kenyon GL. (2003)
Methylene blue as an antimalarial agent. Redox Report 8(5):272-275.
Schirmer RH, Coulibaly B, Stich A, Scheiwein M, Merkle H, Eubel J, Becker K, Becher H, Müller O, Zich T, Schiek W, Kouyaté B. (2003)
Moral und Verteilungsethik des medizinischen Fortschritts. Ethisierung – Ethikferne. Wie viel Ethik braucht die Wissenschaft? (Becker K, Engelen EM, Vec M, Eds) Akademie Verlag Berlin :119-131.
Schirmer H. (2003)
Plasmodium falciparum thioredoxins and glutaredoxins as central players in redox metabolism. Redox Report 8(5):246-50.
Rahlfs S, Nickel Ch, Deponte M, Schirmer RH, Becker K. (2003)
Plasmoredoxin, a novel redox-active protein unique for malarial parasites. Eur J Biochem. 270(6):1057-64.
Becker K, Kanzok SM, Iozef R, Fischer M, Schirmer RH, Rahlfs S. (2003)
The mechanism of high Mr thioredoxin reductase from Drosophila melanogaster. J Biol Chem. 278(35):33020-8.
Bauer H, Massey V, Arscott LD, Schirmer RH, Ballou DP, Williams CH Jr. (2003)
The thioredoxin system - from science to clinic. Med Res Rev. 24:40-89.
Gromer S, Urig S, Becker K. (2003)
Thioredoxin reductase from the malaria mosquito Anopheles gambiae. Eur J Biochem. 270(21):4272-4281.
Bauer H, Gromer S, Urbani A, Schnölzer M, Schirmer RH, Müller HM. (2003)
X-ray structure of glutathione S-transferase from the malarial parasite Plasmodium falciparum. Proc Natl Acad Sci U S A. 100(24):13821-6.
Fritz-Wolf K, Becker A, Rahlfs S, Harwaldt P, Schirmer RH, Kabsch W, Becker K. (2003)
Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite. J Biol Chem 277, 2779-2784
Savvides SN, Scheiwein M, Böhme CC, Arteel GE, Karplus PA, Becker K and Schirmer RH (2002)
Disulfide reductases – current developments. Flavins and Flavoproteins 2002 (Chapman, S.K., Perham, R.N., Scrutton N.S., Eds.) Agency for Scientific Publications Berlin. 803–15. Irmler A, Bechthold A, Davioud-Charvet E, Hofmann V, Réau R, Gromer S, Schirmer RH, Becker K. (2002)
Glutathione Reductase. In: Wiley Encyclopedia of Molecular Medicine (Creighton TE ed) pp 1471-1475 John Wiley & Sons, New York
Schirmer RH, Bauer H & Becker K (2002)
Human placenta thioredoxin reductase: Preparation and inhibitor studies. Meth Enzymol. 347:382-394
Gromer S, Merkle H, Schirmer RH, Becker K. (2002)
Mechanism of high Mr thioredoxin reductase from Drosophila melanogaster. Flavins and Flavoproteins July:131-136
Bauer H, Williams CH Jr, Schirmer RH, Massey V. (2002)
Methylseleninate is a substrate rather than an inhibitor of mammalian thioredoxin reductase. Implications for the antitumour effects of selenium. J Biol Chem 277, 9701-9706
Gromer S & Gross J (2002)
The thioredoxin system of Plasmodium falciparum and other parasites. Cell. Mol. Life Sci. 59:1024-1041
Rahlfs S, Schirmer RH & Becker K. (2002)
Thioredoxin, thioredoxin reductase, and thioredoxin peroxidase of the malaria parasite Plasmodium falciparum. Meth Enzymol 347, 371-381
Kanzok SM, Rahlfs S, Becker K & Schirmer RH (2002)
Thioredoxin-2 but not thioredoxin-1 is a substrate of thioredoxin peroxidase-1 from Drosophila melanogaster. J Biol Chem. 277(20):17457-17463
Bauer H, Kanzok SM, Schirmer RH. (2002)
A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline. J. Med. Chem. 44:4268–76. Davioud-Charvet E, Delarue S, Biot C, Schwöbel B, Böhme CC, Müssigbrodt A, Maes L, Sergheraert C, Grellier P, Schirmer RH, Becker K. (2001)
Medical target prediction from genome sequence: Combining different sequence analysis algorithms with expert knowledge and input from artificial intelligence approaches Comput Chem 26, 15-21
Dandekar T, Du F, Schirmer RH & Schmidt S (2001)
Otto Meyerhof und die Medizin in Heidelberg http://www.uni-heidelberg.de/presse/news/2104meyerhof.html Schirmer RH & Gromer S (2001)
The thioredoxin system substitutes for glutathione reductase in Drosophila melanogaster Science 291, 643-646
Kanzok S, Fechner A, Bauer H, Ulschmid JK, Botella JA, Schneuwly S, Müller HM, Schirmer RH and Becker K (2001)
Thioredoxin reductase:Two modes of catalysis have evolved. Eur J Biochem 167, 6110-6117
Williams, CH Jr, Arscott LD, Müller S, Lennon BW, Ludwig, ML, Wang, PF, Veine D, Becker K & Schirmer RH (2000)
Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 422, 311-314
Färber PM, Arscott LD, Williams CH Jr, Becker K & Schirmer RH (1998)
The mechanism of thioredoxin reductase from human placenta is similar to the mechanism of lipoamide dehydrogenase and glutathione reductase and distinct from that of thioredoxin reductase from Escherichia coli. Proc Natl Acad Sci USA 94, 3126-3626
Arscott LD, Gromer S, Schirmer RH, Becker K & Williams CH Jr. (1997)
Disulfide-reductase inhibitors as chemotherapeutic agents: The design of drugs for trypanosomiasis and malaria. Angew Chem Int Ed Engl 34, 141-154 Schirmer RH, Müller JG & Krauth-Siegel RL (1995)
Principles of Protein Structure, 314 pages, Springer Verlag, New York. Japanese 1979, 1991; Russian 1982. Schulz, G. E., & Schirmer, R. H. (1979)
Topological comparison of adenyl kinase with other proteins. Nature, 250(462), 142–144. Schulz, G. E., & Schirmer, R. H. (1974)
Röseler A, Prieto JH, Iozef R, Hecker B, Schirmer RH, Külzer S, Przyborski J, Rahlfs S, Becker K (2012)
Subcellular localization of adenylate kinases in Plasmodium falciparum. FEBS Lett. 586(19):3037-43.
Ma J, Rahlfs S, Jortzik E, Schirmer RH, Przyborski JM, Becker K (2012)
"Lest we forget you--methylene blue...". Neurobiol Aging. 32(12):2325.e7-16.
Schirmer RH, Adler H, Pickhardt M, Mandelkow E (2011)
Die Entstehung und Entwicklung des Biochemie-Zentrums. in Wissenschaftsatlas der Universität Heidelberg 1386 – 2011, pp. 222-224. BIBLIOTHECA PALATINA Verlag. Schafmeier, T., Franke-Schaub, M., Schirmer, R. H. and Brunner, M. (2011)
Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites. J Am Chem Soc. 133(30):11557-71. Müller T, Johann L, Jannack B, Brückner M, Lanfranchi DA, Bauer H, Sanchez C, Yardley V, Deregnaucourt C, Schrével J, Lanzer M, Schirmer RH, Davioud-Charvet E (2011)
The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue. Redox Rep. 16(4):154-65.
Kasozi DM, Gromer S, Adler H, Zocher K, Rahlfs S, Wittlin S, Fritz-Wolf K, Schirmer RH, Becker K (2011)
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Efficacy of methylene blue monotherapy in semi-immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso. Trop Med Int Health 15(6):713-7.
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Molecular genetics evidence for the in vivo roles of the two major NADPH-dependent disulfide reductases in the malaria parasite. J Biol Chem. 285(48):37388-95.
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Inherited glutathione reductase deficiency and Plasmodium falciparum malaria--a case study. PLoS One. 4(10):e7303.
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Myristoylated adenylate kinase-2 of Plasmodium falciparum forms a heterodimer with myristoyltransferase. Mol Biochem Parasitol. 163(2):77-84.
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NMR assignments of oxidised thioredoxin from Plasmodium falciparum. Biomol NMR Assign. 3(2):159-61.
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Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial. PLoS One. 4(5):e5318.
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Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite. PLoS ONE. 3(6):e2474.
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Disulfide reductases as drug targets: Methylene blue combination therapies for falciparum malaria in African children. (2008) Flavins and Flavoproteins 2008 (Frago S, Gómez-Moreno C, Medina M eds) Prensas Universitarias Zaragoza. 481-486.
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Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS ONE. 3(2):e1630.
Zoungrana A, Coulibaly B, Sié A, Walter-Sack I, Mockenhaupt FP, Kouyaté B, Schirmer RH, Klose C, Mansmann U, Meissner P, Müller O. (2008)
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Attitudes towards colouration effects associated with methylene blue malaria treatment in rural Burkina Faso. Curare 30:27-34.
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Buchholz K, Schirmer RH, Eubel JK, Akoachère MB, Dandekar T, Becker K, Gromer S. (2007)
Kontrolle tropischer Infektionskrankheiten. Multidisziplinäre Forschungsprojekte in Burkina Faso. Flugmedizin, Tropenmedizin, Reisemedizin (FTR) 14: 31-32.
Müller O, Schirmer H. (2007)
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Methylenblau in der Malariatherapie. Eine Alternative für Afrika? Flugmedizin, Tropenmedizin, Reisemedizin (FTR) 14: 33-35.
Müller O, Meissner P, Schirmer RH. (2007)
Molecular basis of glutathione reductase deficiency in human blood cells. Blood 109:3560-3566.
Kamerbeek NM, van Zwieten R, de Boer M, Morren G, Vuil H, Bannink N, Lincke C, Dolman KM, Becker K, Schirmer RH, Gromer S, Roos D. (2007)
A fluoro analogue of the menadione derivative 6-[2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme. J Am Chem Soc. 128(33):10784-94.
Bauer H, Fritz-Wolf K, Winzer A, Kühner S, Little S, Yardley V, Vezin H, Palfey B, Schirmer RH, Davioud-Charvet E. (2006)
Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrob Agents Chemother. 50(9):3132-41.
Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W, Elliott DA, Joiner KA, Schirmer RH, Anderson KS. (2006)
Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malar J. 5:84.
Meissner PE, Mandi G, Coulibaly B, Witte S, Tapsoba T, Mansmann U, Rengelshausen J, Schiek W, Jahn A, Walter-Sack I, Mikus G, Burhenne J, Riedel KD, Schirmer RH, Kouyaté B, Müller O. (2006)
Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein. Nucleic Acids Res. 34(14):4012-24.
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The Plasmodium selenoproteome. Nucleic Acids Res. 34(2):496-505.
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(1)H, (13)C, and (15)N Sequence-specific Resonance Assignment and Secondary Structure of Plasmodium falciparum Thioredoxin. J Biomol NMR. 32(4):340.
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Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts. Biol Chem. 386(1):41-52.
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Comparative structural analysis of oxidized and reduced thioredoxin from Drosophila melanogaster. J Mol Biol. 345(5):1119-30.
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Diagnosis of red cell G6PD deficiency in rural Burkina Faso. Comparison of a rapid fluorescent enzyme test on filter paper with polymerase chain reaction based genotyping. Br J Haematol. 131: 395-9.
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Effects of antioxidants on glutathione levels and clinical recovery from the malnutrition syndrome kwashiorkor - a pilot study. Redox Rep. 10(4):215-26.
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In Vitro Assessment of Methylene Blue on Chloroquine-Sensitive and -Resistant Plasmodium falciparum Strains Reveals Synergistic Action with Artemisinins. Antimicrob Agents Chemother. 49(11):4592-7.
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The conserved histidine 106 of large thioredoxin reductases is likely to have a structural role but not a base catalyst function. FEBS Lett. 579(3):745-8.
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YANA - a software tool for analyzing flux modes, gene-expression and enzyme activities. BMC Bioinformatics. 6(1):135.
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Biochemistry-based health care research. Methylene blue, malaria, methemoglobin, and malnutrition. Health Research in Developing Countries (Becher H, Kouyaté B eds). Springer Verlag, Berlin-Heidelberg. 285-297.
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Pharmacogenomic strategies against resistance development in microbial infections. Pharmacogenomics. 5(4):361-79.
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The thioredoxin system - from science to clinic. Med Res Rev. 24(1):40-89.
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A putative glutathione peroxidase of Drosophila encodes a thioredoxin peroxidase that provides resistance against oxidative stress but fails to complement a lack of catalase activity. Biol Chem. 384:463-472.
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Active sites of thioredoxin reductases: Why selenoproteins? Proc Natl Acad Sci U S A. 100(22):12618-12623
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Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development. J Mol Biol. 328(4):893-907.
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Glutathione-functions and metabolism in the malarial parasite Plasmodium falciparum. Biol Chem. 384(4):551-66.
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Glyoxalase I of the malarial parasite Plasmodium falciparum. Evidence for subunit fusion. FEBS Lett. 554:284-288.
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Mechanism-based inactivation of thioredoxin reductase from Plasmodium falciparum by Mannich bases. Implications for cytotoxicity. Biochemistry 42(45):13319-13330. Davioud-Charvet E, McLeish MJ, Veine DM, Giegel D, Arscott LD, Andricopulo AD, Becker K, Müller S, Schirmer RH, Williams CH Jr, Kenyon GL. (2003)
Methylene blue as an antimalarial agent. Redox Report 8(5):272-275.
Schirmer RH, Coulibaly B, Stich A, Scheiwein M, Merkle H, Eubel J, Becker K, Becher H, Müller O, Zich T, Schiek W, Kouyaté B. (2003)
Moral und Verteilungsethik des medizinischen Fortschritts. Ethisierung – Ethikferne. Wie viel Ethik braucht die Wissenschaft? (Becker K, Engelen EM, Vec M, Eds) Akademie Verlag Berlin :119-131.
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Plasmodium falciparum thioredoxins and glutaredoxins as central players in redox metabolism. Redox Report 8(5):246-50.
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Plasmoredoxin, a novel redox-active protein unique for malarial parasites. Eur J Biochem. 270(6):1057-64.
Becker K, Kanzok SM, Iozef R, Fischer M, Schirmer RH, Rahlfs S. (2003)
The mechanism of high Mr thioredoxin reductase from Drosophila melanogaster. J Biol Chem. 278(35):33020-8.
Bauer H, Massey V, Arscott LD, Schirmer RH, Ballou DP, Williams CH Jr. (2003)
The thioredoxin system - from science to clinic. Med Res Rev. 24:40-89.
Gromer S, Urig S, Becker K. (2003)
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X-ray structure of glutathione S-transferase from the malarial parasite Plasmodium falciparum. Proc Natl Acad Sci U S A. 100(24):13821-6.
Fritz-Wolf K, Becker A, Rahlfs S, Harwaldt P, Schirmer RH, Kabsch W, Becker K. (2003)
Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite. J Biol Chem 277, 2779-2784
Savvides SN, Scheiwein M, Böhme CC, Arteel GE, Karplus PA, Becker K and Schirmer RH (2002)
Disulfide reductases – current developments. Flavins and Flavoproteins 2002 (Chapman, S.K., Perham, R.N., Scrutton N.S., Eds.) Agency for Scientific Publications Berlin. 803–15. Irmler A, Bechthold A, Davioud-Charvet E, Hofmann V, Réau R, Gromer S, Schirmer RH, Becker K. (2002)
Glutathione Reductase. In: Wiley Encyclopedia of Molecular Medicine (Creighton TE ed) pp 1471-1475 John Wiley & Sons, New York
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Human placenta thioredoxin reductase: Preparation and inhibitor studies. Meth Enzymol. 347:382-394
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Mechanism of high Mr thioredoxin reductase from Drosophila melanogaster. Flavins and Flavoproteins July:131-136
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Methylseleninate is a substrate rather than an inhibitor of mammalian thioredoxin reductase. Implications for the antitumour effects of selenium. J Biol Chem 277, 9701-9706
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The thioredoxin system of Plasmodium falciparum and other parasites. Cell. Mol. Life Sci. 59:1024-1041
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Thioredoxin, thioredoxin reductase, and thioredoxin peroxidase of the malaria parasite Plasmodium falciparum. Meth Enzymol 347, 371-381
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Thioredoxin-2 but not thioredoxin-1 is a substrate of thioredoxin peroxidase-1 from Drosophila melanogaster. J Biol Chem. 277(20):17457-17463
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A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline. J. Med. Chem. 44:4268–76. Davioud-Charvet E, Delarue S, Biot C, Schwöbel B, Böhme CC, Müssigbrodt A, Maes L, Sergheraert C, Grellier P, Schirmer RH, Becker K. (2001)
Medical target prediction from genome sequence: Combining different sequence analysis algorithms with expert knowledge and input from artificial intelligence approaches Comput Chem 26, 15-21
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The thioredoxin system substitutes for glutathione reductase in Drosophila melanogaster Science 291, 643-646
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Thioredoxin reductase:Two modes of catalysis have evolved. Eur J Biochem 167, 6110-6117
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Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 422, 311-314
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The mechanism of thioredoxin reductase from human placenta is similar to the mechanism of lipoamide dehydrogenase and glutathione reductase and distinct from that of thioredoxin reductase from Escherichia coli. Proc Natl Acad Sci USA 94, 3126-3626
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Disulfide-reductase inhibitors as chemotherapeutic agents: The design of drugs for trypanosomiasis and malaria. Angew Chem Int Ed Engl 34, 141-154 Schirmer RH, Müller JG & Krauth-Siegel RL (1995)
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Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
