4LCE

CtBP1 in complex with substrate MTOB

Summary for 4LCE

• Entry DOI: 10.2210/pdb4lce/pdb
• Related: 4LCJ
• Descriptor: C-terminal-binding protein 1, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 4-(METHYLSULFANYL)-2-OXOBUTANOIC ACID, ... (4 entities in total)
• Functional Keywords: rossmann fold, transcriptional co-repressor, d-isomer 2-hydroxyacid dehydrogenase, oxidoreductase-oxidoreductase substrate complex, oxidoreductase/oxidoreductase substrate
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q13363
• Total number of polymer chains: 1
• Total formula weight: 38951.07

Authors

Hilbert, B.J.,Schiffer, C.A.,Royer Jr., W.E. (deposition date: 2013-06-21, release date: 2014-03-19, Last modification date: 2024-02-28)

Primary citation

Hilbert, B.J.,Grossmann, S.R.,Schiffer, C.A.,Royer, W.E.
Crystal structures of human CtBP in complex with substrate MTOB reveal active site features useful for inhibitor design.
Febs Lett., 588:1743-1748, 2014

PubMed Abstract: The oncogenic corepressors C-terminal Binding Protein (CtBP) 1 and 2 harbor regulatory d-isomer specific 2-hydroxyacid dehydrogenase (d2-HDH) domains. 4-Methylthio 2-oxobutyric acid (MTOB) exhibits substrate inhibition and can interfere with CtBP oncogenic activity in cell culture and mice. Crystal structures of human CtBP1 and CtBP2 in complex with MTOB and NAD(+) revealed two key features: a conserved tryptophan that likely contributes to substrate specificity and a hydrophilic cavity that links MTOB with an NAD(+) phosphate. Neither feature is present in other d2-HDH enzymes. These structures thus offer key opportunities for the development of highly selective anti-neoplastic CtBP inhibitors.

PubMed: 24657618
DOI: 10.1016/j.febslet.2014.03.026

Experimental method

X-RAY DIFFRACTION (2.38 Å)