کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10870746 1074019 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Crystal structures of human CtBP in complex with substrate MTOB reveal active site features useful for inhibitor design
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
Crystal structures of human CtBP in complex with substrate MTOB reveal active site features useful for inhibitor design
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 588, Issue 9, 2 May 2014, Pages 1743-1748
نویسندگان
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