Reaction: (2R)-2-hydroxy-4-(methylsulfanyl)butanoate + NAD+ = 4-(methylsulfanyl)-2-oxobutanoate + NADH + H+
Other name(s): CTBP1 (gene name); C-terminal-binding protein 1; MTOB reductase; 4-methylthio 2-oxobutyrate reductase; 4-methylthio 2-oxobutyric acid reductase
Systematic name: (2R)-2-hydroxy-4-(methylsulfanyl)butanoate:NAD+ 2-oxidoreductase
Comments: The substrate of this enzyme is formed as an intermediate during L-methionine salvage from S-methyl-5'-thioadenosine, which is formed during the biosynthesis of polyamines. The human enzyme also functions as a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes, thus providing a link between gene repression and the methionine salvage pathway. A similar, but NADP-specific, enzyme is involved in dimethylsulfoniopropanoate biosynthesis in algae and phytoplankton.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Kumar, V., Carlson, J.E., Ohgi, K.A., Edwards, T.A., Rose, D.W., Escalante, C.R., Rosenfeld, M.G. and Aggarwal, A.K. Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase. Mol. Cell 10 (2002) 857-869. [PMID: 12419229]
2. Achouri, Y., Noel, G. and Van Schaftingen, E. 2-Keto-4-methylthiobutyrate, an intermediate in the methionine salvage pathway, is a good substrate for CtBP1. Biochem. Biophys. Res. Commun. 352 (2007) 903-906. [PMID: 17157814]
3. Hilbert, B.J., Grossman, S.R., Schiffer, C.A. and Royer, W.E., Jr. Crystal structures of human CtBP in complex with substrate MTOB reveal active site features useful for inhibitor design. FEBS Lett. 588 (2014) 1743-1748. [PMID: 24657618]
4. Korwar, S., Morris, B.L., Parikh, H.I., Coover, R.A., Doughty, T.W., Love, I.M., Hilbert, B.J., Royer, W.E., Jr., Kellogg, G.E., Grossman, S.R. and Ellis, K.C. Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP). Bioorg. Med. Chem. 24 (2016) 2707-2715. [PMID: 27156192]