Role of NAD binding and catalytic residues in the C-terminal binding protein corepressor.
CtBP corepressor proteins potentiate the activity of many metazoan transcriptional repressors. These proteins are homologous to prokaryotic D-2-hydroxyacid dehydrogenases, possessing an NAD/NADH binding fold and conserved active site residues. When expressed in Drosophila, a catalytic site mutant retains biological activity, however, we find that an NAD binding mutant lacks biological activity. The NAD mutant, similar to a dimerization mutant, is expressed at low levels, indicating that binding of NAD/NADH may affect CtBP stability. These data support the idea that the ancestral dehydrogenase activity is not required for CtBP function, and NAD binding may play a regulatory, rather than catalytic, role.
Mani-Telang
Priya
P
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Sutrias-Grau
Montserrat
M
Williams
Geoffrey
G
Arnosti
David N
DN
D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009243:NAD / Q000378:metabolism*; D010641:Phenotype; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D009243:NAD; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein