Jump to ContentJump to Main Navigation
Show Summary Details

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

IMPACT FACTOR 2015: 2.710
Rank 142 out of 289 in category Biochemistry & Molecular Biology in the 2015 Thomson Reuters Journal Citation Report/Science Edition

SCImago Journal Rank (SJR) 2015: 1.607
Source Normalized Impact per Paper (SNIP) 2015: 0.751
Impact per Publication (IPP) 2015: 2.609

See all formats and pricing
Volume 383, Issue 5 (May 2002)


Glutathione S-Transferase of the Malarial Parasite Plasmodium falciparum: Characterization of a Potential Drug Target

Petra Harwaldt / Stefan Rahlfs / Katja Becker
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2002.086


Glutathione Stransferases (GSTs), which occur abundantly in most organisms, are essentially involved in the intracellular detoxification of numerous substances including chemotherapeutic agents, and thus play a major role in the development of drug resistance. A gene encoding a protein with sequence identity of up to 37% with known GSTs was identified on chromosome 14 of the malarial parasite Plasmodium falciparum. It was amplified using gametocyte cDNA and expressed in Escherichia coli as a hexahistidyltagged protein of 26 kDa subunit size. The homodimeric enzyme (PfGST) was found to catalyse the glutathione (GSH)dependent modification of 1-chloro-2,4-dinitrobenzene and other typical GST substrates such as onitrophenyl acetate, ethacrynic acid, and cumene hydroperoxide. The Km value for GSH was 164±20 M. PfGST was inhibited by cibacron blue (Ki=0.5 M), Shexylglutathione (Ki=35 M), and protoporphyrin IX (Ki=10 M). Hemin, a most toxic compound for parasitised erythrocytes, was found to be an uncompetitive ligand of PfGST with a Ki of 6.5 M. Based on the activity of PfGST in extracts of P. falciparum, the enzyme represents 1 to 10% of cellular protein and might therefore serve as an efficient in vivo buffer for parasitotoxic hemin. Destabilising ligands of GST are thus expected to be synergistic with the antimalarial drug chloroquine, which itself was found to be a very weak inhibitor of PfGST (IC50 >200 M). Xray quality crystals of PfGST (25020050 m) will serve as starting point for structurebased drug design.

About the article

Published Online: 2005-06-01

Published in Print: 2002-05-15

Citation Information: Biological Chemistry, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2002.086. Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Markus Perbandt, Raphael Eberle, Lena Fischer-Riepe, Eva Liebau, and Christian Betzel
Journal of Structural Biology, 2015
Y. Yang, J. Xiong, Z. Zhou, F. Huo, W. Miao, C. Ran, Y. Liu, J. Zhang, J. Feng, M. Wang, M. Wang, L. Wang, and B. Yao
Genome Biology and Evolution, 2014, Volume 6, Number 12, Page 3182
Indalecio Quesada-Soriano, Carmen Barón, Ramiro Téllez-Sanz, Federico García-Maroto, and Luis García-Fuentes
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2014, Volume 1844, Number 9, Page 1427
K. Fritz-Wolf, A. Becker, S. Rahlfs, P. Harwaldt, R. H. Schirmer, W. Kabsch, and K. Becker
Proceedings of the National Academy of Sciences, 2003, Volume 100, Number 24, Page 13821
Umashankar Das, Ravi S.P. Singh, Jane Alcorn, Mark R. Hickman, Richard J. Sciotti, Susan E. Leed, Patricia J. Lee, Norma Roncal, and Jonathan R. Dimmock
Bioorganic & Medicinal Chemistry, 2013, Volume 21, Number 23, Page 7250
Chikezie and Paul Chidoka
Free Radicals and Antioxidants, 2011, Volume 1, Number 2, Page 26
Indalecio Quesada-Soriano, Carmen Barón, Federico García-Maroto, Ana M. Aguilera, and Luís García-Fuentes
Biochemistry, 2013, Volume 52, Number 11, Page 1980
M. K. Cherif, G. S. Sanou, B. Maiga, E. Israelsson, A. L. Ouédraogo, E. C. Bougouma, A. Diarra, A. Ouédraogo, A. S. Ouattara, M. Troye-Blomberg, A. Dolo, D. R. Cavanagh, M. Theisen, D. Modiano, S. B. Sirima, and I. Nebié
Scandinavian Journal of Immunology, 2012, Volume 75, Number 6, Page 606
Timir Tripathi, Byoung-Kuk Na, Woon-Mok Sohn, Katja Becker, and Vinod Bhakuni
Archives of Biochemistry and Biophysics, 2009, Volume 487, Number 2, Page 115
Iqbal Hamza and Harry A. Dailey
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2012, Volume 1823, Number 9, Page 1617
Rimma Iozef, Stefan Rahlfs, Tammy Chang, Heiner Schirmer, and Katja Becker
FEBS Letters, 2003, Volume 554, Number 3, Page 284
G.N. Sarma, S.N. Savvides, K. Becker, M. Schirmer, R.H. Schirmer, and P.A. Karplus
Journal of Molecular Biology, 2003, Volume 328, Number 4, Page 893
Chinmay Pal and Uday Bandyopadhyay
Antioxidants & Redox Signaling, 2012, Volume 17, Number 4, Page 555
Esther Jortzik, Lihui Wang, and Katja Becker
Antioxidants & Redox Signaling, 2012, Volume 17, Number 4, Page 657
Eva-Maria Patzewitz, Eleanor H. Wong, and Sylke Müller
Molecular Microbiology, 2012, Volume 83, Number 2, Page 304
Shamina Azeez, Rosana O. Babu, Riju Aykkal, and Reena Narayanan
Journal of Molecular Modeling, 2012, Volume 18, Number 1, Page 151
Zhengxiang He, Lili Chen, Jianlan You, Li Qin, and Xiaoping Chen
Experimental Parasitology, 2009, Volume 123, Number 2, Page 122
Adele M. Lehane, Christopher A. McDevitt, Kiaran Kirk, and David A. Fidock
International Journal for Parasitology: Drugs and Drug Resistance, 2012, Volume 2, Page 47
Fátima Nogueira, Amalia Diez, Azar Radfar, Susana Pérez-Benavente, Virgilio E. do Rosario, Antonio Puyet, and José M. Bautista
Acta Tropica, 2010, Volume 114, Number 2, Page 109
Athar Alam, Manish Goyal, Mohd Shameel Iqbal, Chinmay Pal, Sumanta Dey, Samik Bindu, Pallab Maity, and Uday Bandyopadhyay
Expert Review of Clinical Pharmacology, 2009, Volume 2, Number 5, Page 469
Nisha Mathew, Lakshmy Srinivasan, Twinkle Karunan, Elango Ayyanar, and Kalyanasundaram Muthuswamy
Journal of Molecular Modeling, 2011, Volume 17, Number 10, Page 2651
Sebastian Kehr, Esther Jortzik, Claire Delahunty, John R. Yates, Stefan Rahlfs, and Katja Becker
Antioxidants & Redox Signaling, 2011, Volume 15, Number 11, Page 2855
Mohammad Sohail, Ritesh Kumar, Asha Kaul, Ehtesham Arif, Sanjit Kumar, and Tridibes Adak
Free Radical Biology and Medicine, 2010, Volume 49, Number 11, Page 1746
Byoung-Kuk Na, Jung-Mi Kang, Tong-Soo Kim, and Woon-Mok Sohn
Experimental Parasitology, 2007, Volume 116, Number 4, Page 414
Sanjay Kumar, Mithu Guha, Vinay Choubey, Pallab Maity, and Uday Bandyopadhyay
Life Sciences, 2007, Volume 80, Number 9, Page 813
Gero Bergner, Christian R. Albert, Markus Schiller, Gerhard Bringmann, Tanja Schirmeister, Benjamin Dietzek, Stephan Niebling, Sebastian Schlücker, and Jürgen Popp
The Analyst, 2011, Volume 136, Number 18, Page 3686
Shu-Chuan Jao, Jessica Chen, Kelvin Yang, and Wen-Shan Li
Bioorganic & Medicinal Chemistry, 2006, Volume 14, Number 2, Page 304
Segun Fatumo, Kitiporn Plaimas, Jan-Philipp Mallm, Gunnar Schramm, Ezekiel Adebiyi, Marcus Oswald, Roland Eils, and Rainer König
Infection, Genetics and Evolution, 2009, Volume 9, Number 3, Page 351
Katja Becker, Leann Tilley, Jonathan L. Vennerstrom, David Roberts, Stephen Rogerson, and Hagai Ginsburg
International Journal for Parasitology, 2004, Volume 34, Number 2, Page 163
Azar Radfar, Amalia Diez, and José M. Bautista
Free Radical Biology and Medicine, 2008, Volume 44, Number 12, Page 2034
K. Becker, S. Rahlfs, C. Nickel, and R. H. Schirmer
Biological Chemistry, 2003, Volume 384, Number 4
Sylke Müller
Molecular Microbiology, 2004, Volume 53, Number 5, Page 1291
Lakshmy Srinivasan, Nisha Mathew, and Kalyanasundaram Muthuswamy
Parasitology Research, 2009, Volume 105, Number 4, Page 1179
Juan R. Rodrigues and Neira D. Gamboa
Parasitology Research, 2009, Volume 104, Number 6, Page 1491
Stefan Rahlfs, Christine Nickel, Marcel Deponte, R. Heiner Schirmer, and Katja Becker
Redox Report, 2003, Volume 8, Number 5, Page 246
Nicole Hiller, Karin Fritz-Wolf, Marcel Deponte, Wolfgang Wende, Herbert Zimmermann, and Katja Becker
Protein Science, 2006, Volume 15, Number 2, Page 281
Nisha Mathew, Muthuswami Kalyanasundaram, and Kothandapani Balaraman
Expert Opinion on Therapeutic Patents, 2006, Volume 16, Number 4, Page 431
Sasa Koncarevic, Ralf Bogumil, and Katja Becker
PROTEOMICS, 2007, Volume 7, Number 5, Page 711
Rumana Ahmad and Arvind K. Srivastava
Parasitology Research, 2006, Volume 100, Number 3, Page 581
Sivaramakrishnan Thirumalai Nathan, Nisha Mathew, Muthuswami Kalyanasundaram, and Kothandapani Balaraman
Journal of Molecular Modeling, 2005, Volume 11, Number 3, Page 194
R. Luise Krauth-Siegel, Holger Bauer, and R. Heiner Schirmer
Angewandte Chemie, 2005, Volume 117, Number 5, Page 698
Katja Becker, Stefan M. Kanzok, Rimma Iozef, Marina Fischer, R. Heiner Schirmer, and Stefan Rahlfs
European Journal of Biochemistry, 2003, Volume 270, Number 6, Page 1057

Comments (0)

Please log in or register to comment.
Log in