title: 2-Keto-4-methylthiobutyrate, an intermediate in the methionine salvage pathway, is a good substrate for CtBP1.
abstract: In the present work, we have studied the kinetic properties of the catalytic domain of CtBP1, a co-repressor belonging to the d-2-hydroxyacid dehydrogenase family and known to reduce pyruvate in the presence of NADH. CtBP1 acted on a variety of alpha-keto acids, for which it displayed biphasic curves with inhibition at elevated concentrations, as observed with other dehydrogenases of the same family. Based on catalytic efficiencies, the best substrate was 2-keto-4-methylthiobutyrate, an intermediate of the methionine salvage pathway. It was about 20-fold better than 2-ketoisocaproate and glyoxylate, and 80-fold better than pyruvate. From these data we conclude that 2-keto-4-methylthiobutyrate may be an important regulator of CtBP activity, possibly linking gene repression to the activity of the methionine salvage and spermine synthesis pathways.
authors.affiliation: Université catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Avenue Hippocrate 75, B-1200 Brussels, Belgium. younes.achouri@bchm.ucl.ac.be
authors.forename: Younes
authors.initials: Y
authors.lastname: Achouri
authors.forename: Gaëtane
authors.initials: G
authors.lastname: Noël
authors.forename: Emile
authors.initials: E
authors.lastname: Van Schaftingen
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D004268:DNA-Binding Proteins; C014632:2-keto-4-methylthiobutyric acid; D008715:Methionine; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein