Research Group Deponte

Research & References

of the Deponte lab

Research: Comparative Biochemistry

The Deponte lab compares enzymes and protein machineries from baker's yeast (Saccharomyces cerevisiae), the kinetoplastid parasite Leishmania tarentolae and the apicomplexan human malaria parasite Plasmodium falciparum. These unicellular organisms are excellent study objects for comparative biochemistry because they belong to three independent eukaryotic lineages and have a completely different lifestyle and biology.

The objective of our organismic triangulation is to decipher:

  • Principles in biochemistry that are common to all eukaryotes.
  • Parasite-specific properties in order to understand what exactly distinguishes these pathogens from yeast or human at the molecular level.

We perform in-depth analyses of enzyme mechanisms and protein structure-function relationships using a variety of methods that range from:

  • Molecular modelling and other bioinformatic analyses in order to develop hypotheses.
  • Steady-state and stopped-flow kinetic measurements with recombinant wild-type and mutant enzymes in vitro.
  • Heterologous complementation assays, plasmid shuffling and/or CRISPR/Cas9 genetics in S. cerevisiae, L. tarentolae and/or P. falciparum.

Current projects

The research concept on comparative biochemistry is currently applied to two major topics: thiol-dependent redox metabolism and mitochondrial protein import. 

  • For example, we assess the catalytic mechanisms of peroxiredoxins and glutaredoxins in living cells using redox-sensitive green fluorescent protein (shown above) in collaboration with Bruce Morgan (Saarbrücken), Jan Riemer (Cologne) and Ana Tomás (Porto).
  • The enzyme kinetics and redox properties of diverse wild-type and mutant glutaredoxins, peroxiredoxins, flavoenzymes and the artemisinin-susceptibility factor kelch13 from P. falciparum are also compared in vitro in order to identify structure-function relationships and mechanistic principles.
  • Protein-protein interactions of mitochondrial protein import machineries are studied by quantitative mass spectrometry in collaboration with Michael Schroda and Timo Mühlhaus (TUK).
  • Membrane proteins are analyzed in collaboration with Sandro Keller (TUK) and Michael Lanzer (Heidelberg).

For further information on these and other topics, please have a look at the list of publications, visit the web page of the DFG priority program 1710 and/or contact Marcel Deponte.

List of Publications

2019
Calabrese G, Peker E, Amponsah PS, Hoehne MN, Riemer T, Mai M, Bienert GP, Deponte M,  Morgan B, Riemer J. (2019) Hyperoxidation of mitochondrial peroxiredoxin limits H2O2-induced cell death in yeast. EMBO J. in press.

Feld K*, Geissel F*, Liedgens L, Schumann R, Specht S, and Deponte M. (2019) Tyrosine substitution of a conserved active site histidine residue activates Plasmodium falciparum peroxiredoxin 6. Protein Sci. 28:100-110.


2018
Roma LP, Deponte M, Riemer J, and Morgan B. (2018) Mechanisms and applications of redox-sensitive GFP-based H2O2 probes. Antioxid. Redox Signal. 29:552-68.

Liedgens L and Deponte M. (2019) The catalytic mechanism of glutaredoxins. In Glutathione 251-261.

Specht S, Liedgens L, Duarte M, Stiegler A, Wirth U, Eberhardt M, Tomás A, Hell K*, and Deponte M*. (2018) A single-cysteine mutant and chimeras of essential Leishmania Erv can complement the loss of Erv1 but not of Mia40 in yeast. Redox Biol. 15:363-74.

Staudacher V, Trujillo M, Diederichs T, Dick TP, Radi R*, Morgan B*, and Deponte M*. (2018) Redox-sensitive GFP fusions for monitoring the catalytic mechanism and inactivation of peroxiredoxins in living cells. Redox Biol. 14:549-56.


2017
Deponte M. (2017) The incomplete glutathione puzzle: Just guessing at numbers and figures? Antioxid. Redox Signal. 27:1130-61.

Wezena CA, Alisch R, Golzmann A, Liedgens L, Staudacher V, Pradel G, and Deponte M. (2017) The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development. Microbial Cell 5:32-41.

Djuika CF*, Staudacher V*, Sanchez CP, Lanzer M, and Deponte M. (2017) Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum. Sci. Rep. 7:4410.

Begas P*, Liedgens L*, Moseler A, Meyer AJ, and Deponte M. (2017) Glutaredoxin catalysis requires two distinct glutathione interaction sites. Nature Commun. 8:14835.

Wezena CA*, Krafczyk J*, Staudacher V, and Deponte M. (2017) Growth inhibitory effects of standard pro- and antioxidants on the human malaria parasite Plasmodium falciparum. Exp. Parasitol.180:64-70.


2016
Wezena CA*, Urscher M*, Vince R, More S, and Deponte M. (2016) Hemolytic and antimalarial effects of tight-binding glyoxalase 1 inhibitors on the host-parasite unit of erythrocytes infected with Plasmodium falciparum. Redox Biol. 8:348-53.


2015
Begas P, Staudacher V, and Deponte M. (2015) Systematic re-evaluation of the bis(2-hydroxyethyl)disulfide (HEDS) assay reveals an alternative mechanism and activity of glutaredoxins. Chem. Science 6:3788-96.

Staudacher V*, Djuika CF*, Koduka J*, Schlossarek S*, Kopp J, Büchler M, Lanzer M, and Deponte M. (2015) Plasmodium falciparum antioxidant protein reveals a novel mechanism for balancing turnover and inactivation of peroxiredoxins. Free Radic. Biol. Med. 85:228-36.

Deponte M and Lillig CH. (2015) Enzymatic control of cysteinyl thiol switches in proteins. Biol. Chem. 396:401-13.

Djuika CF, Huerta-Cepas J, Przyborski JM, Deil S, Sanchez CP, Doerks T, Bork P, Lanzer M, and Deponte M. (2015) Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites. Microbial Cell 2:5-13.


2014
Deponte M. (2014) Glyoxalase systems in malaria parasites. Encyclopedia of Malaria DOI: 10.1007/978-1-4614-8757-9_17-1

Deponte M. (2014) Mitochondrial protein import in malaria parasites. Encyclopedia of Malaria DOI: 10.1007/978-1-4614-8757-9_95-5

Deponte M. (2014) Glyoxalase diversity in parasitic protists. Biochem. Soc. Trans. 42:473-478.


2013
Djuika C, Fiedler S, Schnölzer M, Sanchez C, Lanzer M, and Deponte M. (2013) Plasmodium falciparum antioxidant protein as a model enzyme for a special class of glutaredoxin/glutathione-dependent peroxiredoxins. Biochim. Biophys. Acta 1830:4073-90.

Ehrhardt K, Davioud-Charvet E, Ke H, Vaidya A, Lanzer M, and Deponte M. (2013) The antimalarial activities of methylene blue and the 1,4-naphthoquinone 3-[4-(trifluoromethyl)benzyl]-menadione are not due to inhibition of the mitochondrial electron transport chain. Antimicrob. Agents Chemother. 57:2114-20.

Deponte M. (2013) Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim. Biophys. Acta 1830:3217-66.

Eckers E, Petrungaro C, Groß D, Riemer J, Hell K, and Deponte M. (2013) Divergent molecular evolution of the mitochondrial sulfhydryl:cytochrome c oxidoreductase Erv in opisthokonts and parasitic protists. J. Biol. Chem. 288:2676-88.


2012
Deponte M*, Hoppe HC*, Lee M*, Maier AG*, Richard D*, Rug M*, Spielmann T*, and Przyborski JM*. (2012) Wherever I may roam: Protein and membrane trafficking in P. falciparum-infected red blood cells. Mol. Biochem. Parasitol. 186:95-116.

Eckers E and Deponte M. (2012) No need for labels: The autofluorescence of Leishmania tarentolae mitochondria and the necessity of negative controls. PLOS ONE 7:e47641.

Urscher M, More SS, Alisch R, Vince R, and Deponte M. (2012) Tight-binding inhibitors efficiently inactivate both reaction centers of monomeric Plasmodium falciparum glyoxalase 1. FEBS J. 279:2568-78.

Eckers E, Cyrklaff M, Simpson L, and Deponte M. (2012) Mitochondrial protein import pathways are functionally conserved among eukaryotes despite compositional diversity of the import machineries. Biol. Chem. 393:513-24.

Deponte M. (2012) GFP tagging sheds light on protein translocation: implications for key methods in cell biology. Cell. Mol. Life Sci. 69:1025-33.


2011
Harner M, Neupert W, and Deponte M. (2011) Lateral release of proteins from the TOM complex into the outer membrane of mitochondria. EMBO J. 30:3232-41.

Urscher M, Alisch R, and Deponte M. (2011) The glyoxalase system of malaria parasites- Implications for cell biology and general glyoxalase research. Semin. Cell. Dev. Biol. 22:262-70.


2010
Urscher M, Przyborski JM, Imoto M, and Deponte M. (2010) Distinct subcellular localization in the cytosol and apicoplast, unexpected dimerization, and inhibition of Plasmodium falciparum glyoxalases. Mol. Microbiol. 76:92-103.


2009
Eckers E, Bien M, Stroobant V, Herrmann JM, and Deponte M. (2009) Biochemical characterization of dithiol glutaredoxin 8 from Saccharomyces cerevisiae: The catalytic redox mechanism redux. Biochemistry 48:1410-23.

Sturm N, Jortzik E, Mailu BM, Koncarevic S, Deponte M, Forchhammer K, Rahlfs S, and Becker K. (2009) Identification of proteins targeted by the thioredoxin superfamily in Plasmodium falciparum. PLoS Pathog. 5:e1000383.

Koncarevic S, Rohrbach P, Deponte M, Krohne G, Rahlfs S, and Becker K. (2009) The malarial parasite Plasmodium falciparum imports the human protein peroxiredoxin 2 for peroxide detoxification. PNAS 106:13323-8.

Deponte M and Hell K. (2009) Disulphide bond formation in the intermembrane space of mitochondria. J. Biochem. 146:599-608.

Urscher M and Deponte M. (2009) Plasmodium falciparum glyoxalase II: Theorell-Chance product inhibition patterns, rate-limiting substrate binding via Arg257/Lys260, and unmasking of acid-base catalysis. Biol. Chem. 390:1171-83.


2008
Mesecke N*, Mittler S*, Eckers E*, Herrmann JM, and Deponte M. (2008) Two novel monothiol glutaredoxins from Saccharomyces cerevisiae provide further insights into iron-sulfur cluster binding, oligomerization, and enzymatic activity of glutaredoxins. Biochemistry 47:1452-63.

Mesecke N, Spang A, Deponte M, and Herrmann JM. (2008) A novel group of glutaredoxins in the cis-Golgi critical for oxidative stress resistance. Mol. Biol. Cell 19:2673-80.

Deponte M. (2008) Programmed cell death in protists. Biochim. Biophys. Acta 1783:1396-405.


2007
Deponte M, Sturm N, Mittler S, Harner M, Mack H, and Becker K. (2007) Allosteric coupling of two different functional active sites in monomeric Plasmodium falciparum glyoxalase I. J. Biol. Chem. 282:28419-30.

Deponte M. (2007) In search of Atropos' scissors: severing the life-thread of Plasmodium. In Programmed Cell Death in Protozoa 91-6.

Deponte M, Rahlfs S, Becker K. (2007) Peroxiredoxin systems of protozoal parasites. In Subcellular Biochemistry: Peroxiredoxin Systems 44:219-29


2006
Nickel C, Rahlfs S, Deponte M, Koncarevic S, and Becker K. (2006) Thioredoxin networks in the malarial parasite Plasmodium falciparum.  Antioxid. Redox Signal. 8:1227-39.

Hiller N, Fritz-Wolf K, Deponte M, Wende W, Zimmermann H, and Becker K. (2006) Plasmodium falciparum glutathione S-transferase – structural and mechanistic studies on ligand binding and enzyme inhibition. Protein Science 15:281-9.


2005
Koncarevic S, Deponte M, Fritz-Wolf K, Meyer M, Urig S, Fischer M, Réau R, Davioud-Charvet R, and Becker K. (2005) Mass spectrometric analysis of human glutathione reductase modified by a gold-phosphole inhibitor. In Flavins and Flavoproteins 15:325-30.

Nickel C, Trujillo M, Rahlfs S, Deponte M, Radi R, and Becker K. (2005) Plasmodium falciparum 2-Cys peroxiredoxin reacts with plasmoredoxin and peroxynitrite. Biol. Chem. 386:1129-36.

Deponte M and Becker K. (2005) Glutathione S-transferase from malarial parasites – structural and functional aspects. Methods Enzymol. 401:241-53.

Deponte M, Urig S, Arscott LD, Fritz-Wolf K, Réau R, Herold-Mende C, Koncarevic S, Meyer M, Davioud-Charvet E, Ballou DP, Williams CH, and Becker K. (2005) Mechanistic studies on a novel, highly potent gold-phosphole inhibitor of human glutathione reductase. J. Biol. Chem. 280:20628-37.

Deponte M and Becker K. (2005) Biochemical characterization of Toxoplasma gondii 1-Cys peroxiredoxin 2 with mechanistic similarities to typical 2-Cys Prx. Mol. Biochem. Parasitol. 140:87-96.

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

Deponte M, Becker K, and Rahlfs S. (2005) Plasmodium falciparum glutaredoxin-like proteins. Biol. Chem. 386:33-40.


2004
Deponte M and Becker K. (2004) Plasmodium falciparum - do killers commit suicide? Trends Parasitol. 20:165-9.


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

Deponte M and Becker-Brandenburg K. (2003) Web Site: Malaria: A Parasite Goes Online. Angew. Chem. Int. Ed. Engl. 42:5266.

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