Crystal structures of human CtBP in complex with substrate MTOB reveal active site features useful for inhibitor design.
FEBS Lett
; 588(9): 1743-8, 2014 May 02.
Article
em En
| MEDLINE
| ID: mdl-24657618
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.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a DNA
/
Oxirredutases do Álcool
/
Metionina
/
Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos