Journal article

Publication year: 2005

Pages: 41-52

Journal: Biological Chemistry

Volume number: 386

Issue number: 1

ISSN: 1431-6730

eISSN: 1437-4315

DOI Link: https://doi.org/10.1515/BC.2005.006

Publisher: De Gruyter Brill

Abstract: 
The glyoxalase system consisting of glyoxalase I (GloI) and glyoxalase II (GloII) constitutes a glutathione-dependent intracellular pathway converting toxic 2-oxoaldehydes, such as methylglyoxal, to the corresponding 2-hydroxyacids. Here we describe a complete glyoxalase system in the malarial parasite Plasmodium falciparum. The biochemical, kinetic and structural properties of cytosolic GloI (cGloI) and two GloIIs (cytosolic GloII named cGloII, and tGloII preceded by a targeting sequence) were directly compared with the respective isofunctional host enzymes. cGloI and cGloII exhibit lower Km values and higher catalytic efficiencies (k(cat)/K-m) than the human counterparts, pointing to the importance of the system in malarial parasites. A Tyr185Phe mutant of cGloII shows a 2.5-fold increase in Km, proving the contribution of Tyr185 to substrate binding. Molecular models suggest very similar active sites/metal binding sites of parasite and host cell enzymes. However, a fourth protein, which has highest similarities to GloI, was found to be unique for malarial parasites; it is likely to act in the apicoplast, and has as yet undefined substrate specificity. Various S-(N-hydroxy-N-arylcarbamoyl)glutathiones tested as P. falciparum Glo inhibitors were active in the lower nanomolar range. The Glo system of Plasmodium will be further evaluated as a target for the development of antimalarial drugs.

Harvard Citation style: Akoachere, M., Iozef, R., Rahlfs, S., Deponte, M., Mannervik, B., Creighton, D., et al. (2005) Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts, Biological Chemistry, 386(1), pp. 41-52. https://doi.org/10.1515/BC.2005.006

APA Citation style: Akoachere, M., Iozef, R., Rahlfs, S., Deponte, M., Mannervik, B., Creighton, D., Schirmer, H., & Becker, K. (2005). Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts. Biological Chemistry. 386(1), 41-52. https://doi.org/10.1515/BC.2005.006