powered by multiNETT - Internet-Systementwicklung
HEIDELBERG UNIVERSITY

Schirmer 
Protein networks that maintain redox homeostasis in malaria parasites and their hosts. Pathophysiology and drug therapy.

Groupleader: Heiner Schirmer
Informationen

2012
Ma J, Rahlfs S, Jortzik E, Schirmer RH, Przyborski JM, Becker K. Subcellular localization of adenylate kinases in Plasmodium falciparum.
FEBS Lett. 2012; 586(19):3037-43.

Röseler A, Prieto JH, Iozef R, Hecker B, Schirmer RH, Külzer S, Przyborski J, Rahlfs S, Becker K. Insight into the selenoproteome of the malaria parasite Plasmodium falciparum.
Antioxid Redox Signal. 2012; 17(4):534-43.

2011
Kasozi DM, Gromer S, Adler H, Zocher K, Rahlfs S, Wittlin S, Fritz-Wolf K, Schirmer RH, Becker K. The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue.
Redox Rep. 2011; 16(4):154-65.

Schirmer RH, Adler H, Pickhardt M, Mandelkow E. "Lest we forget you--methylene blue...".
Neurobiol Aging. 2011; 32(12):2325.e7-16.

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. 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. 2011; 133(30):11557-71.

Meissner P, Adler H, Kasozi D,  Fritz-Wolf K, Schirmer RH. 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   

Schafmeier T, Franke-Schaub M, Schirmer RH, Brunner M. Die Entstehung und Entwicklung des Biochemie-Zentrums.
Wissenschaftsatlas der Universität Heidelberg 1386 – 2011 pp. 222-224, BIBLIOTHECA PALATINA Verlag, Knittlingen

2010
Buchholz K, Putrianti ED, Rahlfs S, Schirmer RH, Becker K, Matuschewski K. Molecular genetics evidence for the in vivo roles of the two major NADPH-dependent disulfide reductases in the malaria parasite.
J Biol Chem. 2010; 285(48):37388-95.

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. Efficacy of methylene blue monotherapy in semi-immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso.
Trop Med Int Health 2010; 15(6):713-7.

2009
Munte CE, Becker K, Schirmer RH, Kalbitzer HR. NMR assignments of oxidised thioredoxin from Plasmodium falciparum.
Biomol NMR Assign. 2009; 3(2):159-61.

Müller O, Sié A, Meissner P, Schirmer RH, Kouyaté B. Artemisinin resistance on the Thai-Cambodian border.
Lancet. 2009; 374(9699):1419.

Gallo V, Schwarzer E, Rahlfs S, Schirmer RH, van Zwieten R, Roos D, Arese P, Becker K. Inherited glutathione reductase deficiency and Plasmodium falciparum malaria--a case study.
PLoS One. 2009; 4(10):e7303.

Xiao K, Jehle F, Peters C, Reinheckel T, Schirmer RH, Dandekar T. CA/C1 peptidases of the malaria parasites Plasmodium falciparum and P. berghei and their mammalian hosts--a bioinformatical analysis.
Biol Chem. 2009; 390(11):1185-97.

Coulibaly B, Zoungrana A, Mockenhaupt FP, Schirmer RH, Klose C, Mansmann U, Meissner PE, Müller O. Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial.
PLoS One. 2009; 4(5):e5318.

Rahlfs S, Koncarevic S, Iozef R, Mailu BM, Savvides SN, Schirmer RH, Becker K. Myristoylated adenylate kinase-2 of Plasmodium falciparum forms a heterodimer with myristoyltransferase.
Mol Biochem Parasitol. 2009; 163(2):77-84.

Schirmer H. Essay on the Medical History of Methylene Blue. http://www.alzforum.org/new/Schirmer.asp
Alzheimer Research Forum 2009.

2008
Buchholz K, Schirmer RH, Eubel JK, Akoachere MB, Dandekar T, Becker K, Gromer S. Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum.
Antimicrob Agents Chemother. 2008; 52(1):183-91.

Zoungrana A, Coulibaly B, Sié A, Walter-Sack I, Mockenhaupt FP, Kouyaté B, Schirmer RH, Klose C, Mansmann U, Meissner P, Müller O. Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso.
PLoS ONE. 2008; 3(2):e1630.

Buchholz K, Comini MA, Wissenbach D, Schirmer RH, Krauth-Siegel RL, Gromer S. Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products.
Mol Biochem Parasitol. 2008; 160(1):65-9.

Buchholz K, Rahlfs S, Schirmer RH, Becker K, Matuschewski K. Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.
PLoS ONE. 2008; 3(6):e2474.

Schirmer RH, Adler H, Zappe HA, Gromer S, Becker K, Coulibaly B, Meissner P (2008) Disulfide reductases as drug targets: Methylene blue combination therapies for falciparum malaria in African children.
Flavins and Flavoproteins 2008 (Frago S, Gómez-Moreno C, Medina M eds) Prensas Universitarias Zaragoza. 2008; 481-486.

Schirmer H. Book Review on KC Nicolaou and T Montagnon. Molecules that changed the world.
J Lab Med 2008; 32:382-383.

2007
Sanon M, Mandi G, De Allegri M, Schirmer H, Meissner P, Müller O. Attitudes towards colouration effects associated with methylene blue malaria treatment in rural Burkina Faso.
Curare 2007, 30:27-34.

Becker K, Schirmer RH. Antioxidative Enzyme des Malariaerregers als Drug Targets.
BIOspektrum 2007,13:138-141.

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. Molecular basis of glutathione reductase deficiency in human blood cells.
Blood 2007, 109:3560-3566.

Müller O, Schirmer H. Kontrolle tropischer Infektionskrankheiten. Multidisziplinäre Forschungsprojekte in Burkina Faso.
Flugmedizin, Tropenmedizin, Reisemedizin (FTR) 2007, 14: 31-32.

Müller O, Meissner P, Schirmer RH. Methylenblau in der Malariatherapie. Eine Alternative für Afrika?
Flugmedizin, Tropenmedizin, Reisemedizin (FTR) 2007, 14: 33-35.

Rosskopf K, Schirmer H. Malaria ist kein Tabu mehr.
Focus Campus 2007, 20:52-55.

Buchholz K, Schirmer RH, Eubel JK, Akoachère MB, Dandekar T, Becker K, Gromer S. Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum.
Antimicrob Agents Chemother Epub 2007

2006
Bauer H, Fritz-Wolf K, Winzer A, Kühner S, Little S, Yardley V, Vezin H, Palfey B, Schirmer RH, Davioud-Charvet E. 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. 2006, 128(33):10784-94.

Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W, Elliott DA, Joiner KA, Schirmer RH, Anderson KS. Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum.
Antimicrob Agents Chemother. 2006, 50(9):3132-41.

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. Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine.
Malar J. 2006, 5:84.

Lobanov AV, Gromer S, Salinas G, Gladyshev VN. Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein.
Nucleic Acids Res. 2006, 34(14):4012-24.

Lobanov AV, Delgado C, Rahlfs S, Novoselov SV, Kryukov GV, Gromer S, Hatfield DL, Becker K, Gladyshev VN. The Plasmodium selenoproteome.
Nucleic Acids Res. 2006, 34(2):496-505.

2005
Akoachere M, Buchholz K, Fischer E, Burhenne J, Haefeli WE, Schirmer RH, Becker K. In Vitro Assessment of Methylene Blue on Chloroquine-Sensitive and -Resistant Plasmodium falciparum Strains Reveals Synergistic Action with Artemisinins.
Antimicrob Agents Chemother. 2005, 49(11):4592-7.

Millet R, Urig S, Jacob J, Amtmann E, Moulinoux JP, Gromer S, Becker K, Davioud-Charvet E. Synthesis of 5-nitro-2-furancarbohydrazides and their cis-diamminedichloroplatinum complexes as bitopic and irreversible human thioredoxin reductase inhibitors.
J Med Chem. 2005, 48(22):7024-39.

Gromer S, Eubel JK, Lee BL, Jacob J. Human selenoproteins at a glance.
Cell Mol Life Sci. 2005, 62: 2414-37.

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. Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841].
Malar J. 2005, 4:45.

Schwarz R, Musch P, von Kamp A, Engels B, Schirmer H, Schuster S, Dandekar T. YANA - a software tool for analyzing flux modes, gene-expression and enzyme activities.
BMC Bioinformatics. 2005, 6(1):135.

Wahl MC, Irmler A, Hecker B, Schirmer RH, Becker K. Comparative structural analysis of oxidized and reduced thioredoxin from Drosophila melanogaster.
J Mol Biol. 2005, 345(5):1119-30.

Munte CE, Becker K, Schirmer RH, Kalbitzer HR. (1)H, (13)C, and (15)N Sequence-specific Resonance Assignment and Secondary Structure of Plasmodium falciparum Thioredoxin.
J Biomol NMR. 2005, 32(4):340.

Becker K, Pons-Kühnemann J, Fechner A, Funk M, Gromer S, Gross HJ, Grünert A, Schirmer RH. Effects of antioxidants on glutathione levels and clinical recovery from the malnutrition syndrome kwashiorkor - a pilot study.
Redox Rep. 2005, 10(4):215-26.

Jacob J, Schirmer RH, Gromer S. The conserved histidine 106 of large thioredoxin reductases is likely to have a structural role but not a base catalyst function.
FEBS Lett. 2005, 579(3):745-8.

Akoachere M, Iozef R, Rahlfs S, Deponte M, Mannervik B, Creighton DJ, Schirmer H, Becker K. Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts.
Biol Chem. 2005, 386(1):41-52.

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. Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso. Trop Med Int Health. 2005, 10(1):32-8.

Krauth-Siegel RL, Bauer H, Schirmer RH. Dithiolproteine als Hüter des intrazellulären Redoxmilieus bei Parasiten: alte und neue Wirkstoff-Targets bei Trypanosomiasis und Malaria.
Angew Chem. 2005, 117:698-724.

Krauth-Siegel RL, Bauer H, Schirmer RH. 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. 2005, 44(5):690-715.

Schirmer RH. Die große Schande.
Frank Rund Plus. 2005, 272: 23.

Meissner PE, Coulibaly B, Mandi G, Mansmann U, Witte S, Schiek W, Müller O, Schirmer RH, Mockenhaupt FP, Bienzle U. 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. 2005, 131: 395-9.

Gromer S, Jacob J, Schirmer RH. Large thioredoxin reductases – A fairy tail story. Flavins and Flavoproteins 2005 (Nishino T, Miura R, Tanokura M, Fukui K Ed)
ArchiTect Inc Tokyo. 2005, 295-306.

2004
Biot C, Bauer H, Schirmer RH, Davioud-Charvet E. 5-substituted tetrazoles as bioisosteres of carboxylic acids. Bioisosterism and mechanistic studies on glutathione reductase inhibitors as antimalarials.
J Med Chem. 2004, 47(24):5972-83.

Ulschmid JK, Rahlfs S, Schirmer RH, Becker K. Adenylate kinase and GTP:AMP phosphotransferase of the malarial parasite Plasmodium falciparum. Central players in cellular energy metabolism.
Mol Biochem Parasitol. 2004, 136(2):211-20.

Gromer S, Urig S, Becker K. The thioredoxin system - from science to clinic.
Med Res Rev. 2004, 24(1):40-89.

Ziebuhr W, Xiao K, Coulibaly B, Schwarz R, Dandekar T. Pharmacogenomic strategies against resistance development in microbial infections.
Pharmacogenomics. 2004, 5(4):361-79.

Coulibaly B, Eubel J, Gromer S, Schirmer RH. 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. 2004, 285-297.

Schirmer H, Medikamente für die Armen - Die Biomedizin des 21. Jahrhunderts darf nicht nur für die Minderheit der Wohlhabenden forschen.
Spektrum der Wissenschaft. 2004, 110-113.

Steiner M, Schmidt H, Lindahl S, Kossel AH, Schuff-Werner P, Schirmer H. Die Entdeckung der Nukleinsäure-Bausteine: ein Beitrag zum 150. Geburtstag Albrecht Kossels, Nobelpreisträger für Physiologie oder Medizin 1910.
Klinische Chemie Mitteilungen. 2004, 35(3/4):46-54.

2003
Gromer S, Urig S, Becker K. The thioredoxin system - from science to clinic.
Med Res Rev. 2003, 24:40-89.

Schirmer RH, Coulibaly B, Stich A, Scheiwein M, Merkle H, Eubel J, Becker K, Becher H, Müller O, Zich T, Schiek W, Kouyaté B. Methylene blue as an antimalarial agent.
Redox Report 2003, 8(5):272-275.

Rahlfs S, Nickel Ch, Deponte M, Schirmer RH, Becker K. Plasmodium falciparum thioredoxins and glutaredoxins as central players in redox metabolism.
Redox Report 2003, 8(5):246-50.

Iozef R, Rahlfs R, Chang T, Schirmer RH, Becker K. Glyoxalase I of the malarial parasite Plasmodium falciparum. Evidence for subunit fusion.
FEBS Lett. 2003, 554:284-288.

Davioud-Charvet E, McLeish MJ, Veine DM, Giegel D, Arscott LD, Andricopulo AD, Becker K, Müller S, Schirmer RH, Williams CH Jr, Kenyon GL. Mechanism-based inactivation of thioredoxin reductase from Plasmodium falciparum by Mannich bases. Implications for cytotoxicity. Biochemistry 2003, 42(45):13319-13330.

Fritz-Wolf K, Becker A, Rahlfs S, Harwaldt P, Schirmer RH, Kabsch W, Becker K. X-ray structure of glutathione S-transferase from the malarial parasite Plasmodium falciparum.
Proc Natl Acad Sci U S A. 2003, 100(24):13821-6.

Bauer H, Gromer S, Urbani A, Schnölzer M, Schirmer RH, Müller HM. Thioredoxin reductase from the malaria mosquito Anopheles gambiae.
Eur J Biochem. 2003, 270(21):4272-4281.

Gromer S, Johannson L, Bauer H, Arscott LD, Rauch S, Ballou D, Williams CH Jr, Schirmer RH, Arnér ESJ. Active sites of thioredoxin reductases: Why selenoproteins?
Proc Natl Acad Sci U S A. 2003, 100(22):12618-12623

Missirlis F, Rahlfs S, Dimopoulos N, Bauer H, Becker K, Hilliker A, Phillips JP, Jäckle H. 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. 2003, 384:463-472.

Bauer H, Massey V, Arscott LD, Schirmer RH, Ballou DP, Williams CH Jr. The mechanism of high Mr thioredoxin reductase from Drosophila melanogaster.
J Biol Chem. 2003, 278(35):33020-8.

Becker K, Rahlfs S, Nickel C, Schirmer RH. Glutathione-functions and metabolism in the malarial parasite Plasmodium falciparum.
Biol Chem. 2003, 384(4):551-66.

Sarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, Karplus PA. Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development.
J Mol Biol. 2003, 328(4):893-907.

Becker K, Kanzok SM, Iozef R, Fischer M, Schirmer RH, Rahlfs S. Plasmoredoxin, a novel redox-active protein unique for malarial parasites.
Eur J Biochem. 2003, 270(6):1057-64.

Schirmer H. Moral und Verteilungsethik des medizinischen Fortschritts.
Ethisierung – Ethikferne. Wie viel Ethik braucht die Wissenschaft? (Becker K, Engelen EM, Vec M, Eds)
Akademie Verlag Berlin 2003, :119-131.

2002
Gromer S, Merkle H, Schirmer RH, Becker K. Human placenta thioredoxin reductase: Preparation and inhibitor studies.
Meth Enzymol. 2002, 347:382-394

Bauer H, Kanzok SM, Schirmer RH. 2002. Thioredoxin-2 but not thioredoxin-1 is a substrate of thioredoxin peroxidase-1 from Drosophila melanogaster.
J Biol Chem. 2002, 277(20):17457-17463

Rahlfs S, Schirmer RH & Becker K. The thioredoxin system of Plasmodium falciparum and other parasites.
Cell. Mol. Life Sci. 2002, 59:1024-1041

Bauer H, Williams CH Jr, Schirmer RH, Massey V. Mechanism of high Mr thioredoxin reductase from Drosophila melanogaster.
Flavins and Flavoproteins 2002, July:131-136

Irmler A, Bechthold A, Davioud-Charvet E, Hofmann V, Réau R, Gromer S, Schirmer RH, Becker K. Disulfide reductases – current developments.
Flavins and Flavoproteins. 2002:803-815

Davioud-Charvet E, McLeish MJ, Veine D, Giegel D, Andricopulo AD, Becker K, Müller S, Schirmer RH, Williams CH Jr, Kenyon GL. Mechanism-based inactivation of thioredoxin reductase from Plasmodium falciparum by Mannich bases. Implications for drug design.
Flavins and Flavoproteins. 2002:845-851

Savvides SN, Scheiwein M, Böhme CC, Arteel GE, Karplus PA, Becker K and Schirmer RH (2002)
Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite.
J Biol Chem 277, 2779-2784

Kanzok SM, Rahlfs S, Becker K & Schirmer RH (2002)
Thioredoxin, thioredoxin reductase, and thioredoxin peroxidase of the malaria parasite Plasmodium falciparum.
Meth Enzymol 347, 371-381

Schirmer RH (2002)
Moral und Verteilungsethik des medizinischen Fortschritts
In: Wieviel Ethik braucht die Wissenschaft?
JABB Leopoldina, Berlin, in press

Schirmer RH, Bauer H & Becker K (2002)
Glutathione Reductase.
In: Wiley Encyclopedia of Molecular Medicine (Creighton TE ed) pp 1471-1475 John Wiley & Sons, New York

Gromer S & Gross J (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

2002
Schirmer RH & Gromer S (2001)
Otto Meyerhof und die Medizin in Heidelberg
http://www.uni-heidelberg.de/presse/news/2104meyerhof.html

2001
Kanzok S, Fechner A, Bauer H, Ulschmid JK, Botella JA, Schneuwly S, Müller HM, Schirmer RH and Becker K (2001)
The thioredoxin system substitutes for glutathione reductase in Drosophila melanogaster
Science 291, 643-646

Davioud-Charvet E, Delarue S, Biot C, Schwöbel B, Böhme CC, Müssigbrodt A, Maes L, Sergheraert C, Grellier P, Schirmer RH and Katja Becker K (2001)
A prodrug form of a Plasmodium falciparum glutathione reductase inhibitor conjugated with a 4-anilinoquinoline.
J Med Chem 44, 4268-4276

Dandekar T, Du F, Schirmer RH & Schmidt S (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

2000
Williams, CH Jr, Arscott LD, Müller S, Lennon BW, Ludwig, ML, Wang, PF, Veine D, Becker K & Schirmer RH (2000) Thioredoxin reductase:Two modes of catalysis have evolved.
Eur J Biochem 167, 6110-6117

1998
Färber PM, Arscott LD, Williams CH Jr, Becker K & Schirmer RH (1998)
Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue.
FEBS Lett. 422, 311-314

1997
Arscott LD, Gromer S, Schirmer RH, Becker K & Williams CH Jr. (1997)
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

1995
Schirmer RH, Müller JG & Krauth-Siegel RL (1995)
Disulfide-reductase inhibitors as chemotherapeutic agents: The design of drugs for trypanosomiasis and malaria.
Angew Chem Int Ed Engl 34, 141-154

weitere. . .
Schulz GE & Schirmer RH (1978, 1981...1999)
Principles of Protein Structure, 314 pages,
Springer Verlag, New York
Japanese 1979, 1991; Russian 1982

Schulz GE & Schirmer RH (1974)
Topological comparison of adenyl kinase with other proteins.
Nature 250, 142-144