4LCE

CtBP1 in complex with substrate MTOB

4LCE の概要

• エントリーDOI: 10.2210/pdb4lce/pdb
• 関連するPDBエントリー: 4LCJ
• 分子名称: C-terminal-binding protein 1, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 4-(METHYLSULFANYL)-2-OXOBUTANOIC ACID, ... (4 entities in total)
• 機能のキーワード: rossmann fold, transcriptional co-repressor, d-isomer 2-hydroxyacid dehydrogenase, oxidoreductase-oxidoreductase substrate complex, oxidoreductase/oxidoreductase substrate
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q13363
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38951.07

構造登録者

Hilbert, B.J.,Schiffer, C.A.,Royer Jr., W.E. (登録日: 2013-06-21, 公開日: 2014-03-19, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.38 Å)