%0 Journal Article %1 Deponte.20070928 %A Deponte, Marcel %A Sturm, Nicole %A Mittler, Sarah %A Harner, Max %A Mack, Hildegard %A Becker, Katja %D 2007/09/28/ %J J Biol Chem %K Allosteric_Regulation Animals Bacteria Binding_Sites Drug_Design Enzyme_Inhibitors Falciparum Glutathione Humans IFZ Kinetics Lactoylglutathione_Lyase Malaria Plasmodium_falciparum Protozoan_Proteins Pyruvaldehyde Recombinant_Proteins Species_Specificity Structure-Activity_Relationship Yeasts %N 39 %P 28419-28430 %T Allosteric coupling of two different functional active sites in monomeric Plasmodium falciparum glyoxalase I %V 282 %X Glyoxalase I (GloI) catalyzes the glutathione-dependent conversion of 2-oxoaldehydes to S-2-hydroxyacylglutathione derivatives. Studies on GloI from diverse organisms such as man, bacteria, yeast, and different parasites show striking differences among these potentially isofunctional enzymes as far as metal content and the number of active sites per subunit are concerned. So far, it is not known whether this structural variability is linked to catalytic or regulatory features in vivo. Here we show that recombinant GloI from the malaria parasite Plasmodium falciparum has a high- and a low-affinity binding site for the diastereomeric hemithioacetals formed by addition of glutathione to methylglyoxal. Both active sites of the monomeric enzyme are functional and have similar k(cat)(app) values. Proteolytic susceptibility studies and detailed analyses of the steady-state kinetics of active-site mutants suggest that both reaction centers can adopt two discrete conformations and are allosteri

@article{Deponte.20070928, abstract = {Glyoxalase I (GloI) catalyzes the glutathione-dependent conversion of 2-oxoaldehydes to S-2-hydroxyacylglutathione derivatives. Studies on GloI from diverse organisms such as man, bacteria, yeast, and different parasites show striking differences among these potentially isofunctional enzymes as far as metal content and the number of active sites per subunit are concerned. So far, it is not known whether this structural variability is linked to catalytic or regulatory features in vivo. Here we show that recombinant GloI from the malaria parasite Plasmodium falciparum has a high- and a low-affinity binding site for the diastereomeric hemithioacetals formed by addition of glutathione to methylglyoxal. Both active sites of the monomeric enzyme are functional and have similar k(cat)(app) values. Proteolytic susceptibility studies and detailed analyses of the steady-state kinetics of active-site mutants suggest that both reaction centers can adopt two discrete conformations and are allosteri}, added-at = {2008-10-14T16:07:18.000+0200}, author = {Deponte, Marcel and Sturm, Nicole and Mittler, Sarah and Harner, Max and Mack, Hildegard and Becker, Katja}, biburl = {https://www.bibsonomy.org/bibtex/2bc09854c1f58828be833d172d10fe684/nutribiochem}, interhash = {b54c6f6b174c37fb37e6138b6b8d3c5b}, intrahash = {bc09854c1f58828be833d172d10fe684}, journal = {J Biol Chem}, keywords = {Allosteric_Regulation Animals Bacteria Binding_Sites Drug_Design Enzyme_Inhibitors Falciparum Glutathione Humans IFZ Kinetics Lactoylglutathione_Lyase Malaria Plasmodium_falciparum Protozoan_Proteins Pyruvaldehyde Recombinant_Proteins Species_Specificity Structure-Activity_Relationship Yeasts}, number = 39, pages = {28419-28430}, timestamp = {2008-10-14T16:08:42.000+0200}, title = {Allosteric coupling of two different functional active sites in monomeric Plasmodium falciparum glyoxalase I}, volume = 282, year = {2007/09/28/} }