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Plasmodium falciparum antioxidant protein reveals a novel mechanism for balancing turnover and inactivation of peroxiredoxins.

Staudacher V, Djuika CF, Koduka J, Schlossarek S, Kopp J, Büchler M, Lanzer M, Deponte M
Free Radic Biol Med 85 228-36 (2015)
Cited: 10 times
EuropePMC logo PMID: 25952724

Abstract

Life under aerobic conditions has shaped peroxiredoxins (Prx) as ubiquitous thiol-dependent hydroperoxidases and redox sensors. Structural features that balance the catalytically active or inactive redox states of Prx, and, therefore, their hydroperoxidase or sensor function, have so far been analyzed predominantly for Prx1-type enzymes. Here we identify and characterize two modulatory residues of the Prx5-type model enzyme PfAOP from the malaria parasite Plasmodium falciparum. Gain- and loss-of-function mutants reveal a correlation between the enzyme parameters and the inactivation susceptibility of PfAOP with the size of residue 109 and the presence or absence of a catalytically relevant but nonessential cysteine residue. Based on our kinetic data and the crystal structure of PfAOP(L109M), we suggest a novel mechanism for balancing the hydroperoxidase activity and inactivation susceptibility of Prx5-type enzymes. Our study provides unexpected insights into Prx structure-function relationships and contributes to our understanding of what makes Prx good enzymes or redox sensors.

Reviews - 4d73 mentioned but not cited (1)

  1. Cysteine Oxidation in Proteins: Structure, Biophysics, and Simulation. Garrido Ruiz D, Sandoval-Perez A, Rangarajan AV, Gunderson EL, Jacobson MP. Biochemistry 61 2165-2176 (2022)

Articles - 4d73 mentioned but not cited (1)

  1. In silico prediction and in vitro assessment of novel heterocyclics with antimalarial activity. Orozco MI, Moreno P, Guevara M, Abonia R, Quiroga J, Insuasty B, Barreto M, Burbano ME, Crespo-Ortiz MDP. Parasitol Res 123 75 (2023)


Reviews citing this publication (1)

  1. The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures? Deponte M. Antioxid Redox Signal 27 1130-1161 (2017)

Articles citing this publication (7)

  1. Hyperoxidation of mitochondrial peroxiredoxin limits H2 O2 -induced cell death in yeast. Calabrese G, Peker E, Amponsah PS, Hoehne MN, Riemer T, Mai M, Bienert GP, Deponte M, Morgan B, Riemer J. EMBO J 38 e101552 (2019)
  2. Redox-sensitive GFP fusions for monitoring the catalytic mechanism and inactivation of peroxiredoxins in living cells. Staudacher V, Trujillo M, Diederichs T, Dick TP, Radi R, Morgan B, Deponte M. Redox Biol 14 549-556 (2018)
  3. Experimentally Dissecting the Origins of Peroxiredoxin Catalysis. Nelson KJ, Perkins A, Van Swearingen AED, Hartman S, Brereton AE, Parsonage D, Salsbury FR, Karplus PA, Poole LB. Antioxid Redox Signal 28 521-536 (2018)
  4. Growth inhibitory effects of standard pro- and antioxidants on the human malaria parasite Plasmodium falciparum. Wezena CA, Krafczyk J, Staudacher V, Deponte M. Exp Parasitol 180 64-70 (2017)
  5. Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum. Djuika CF, Staudacher V, Sanchez CP, Lanzer M, Deponte M. Sci Rep 7 4410 (2017)
  6. Tyrosine substitution of a conserved active-site histidine residue activates Plasmodium falciparum peroxiredoxin 6. Feld K, Geissel F, Liedgens L, Schumann R, Specht S, Deponte M. Protein Sci 28 100-110 (2019)
  7. Characterization of the glutathione-dependent reduction of the peroxiredoxin 5 homolog PfAOP from Plasmodium falciparum. Schumann R, Lang L, Deponte M. Protein Sci 31 e4290 (2022)


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