کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10748662 1050277 2016 26 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A crucial role of Cys218 in configuring an unprecedented auto-inhibition form of MAP2K7
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A crucial role of Cys218 in configuring an unprecedented auto-inhibition form of MAP2K7
چکیده انگلیسی
Mitogen-activated protein kinase kinase 7 (MAP2K7) is an indispensable kinase of the c-Jun N-terminal kinase signal cascade and is rigorously regulated via phosphorylation. To investigate the regulatory mechanism of the inactive non-phosphorylated state of MAP2K7, the crystal structures of the wild-type and C218S mutant were solved. The wild-type apo-structure revealed an unprecedented auto-inhibition form that occluded the ATP site. This closed form was configured by the n-σ* interaction of Cys218, a non-conserved residue among the MAP2K family kinases, with Gly145 in the glycine-rich loop. The interaction was unaltered in the presence of an ATP analog, whereas the C218S mutation precluded the closed configuration. These structural insights are potentially valuable for drug discovery of highly selective MAP2K7 inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 473, Issue 2, 29 April 2016, Pages 476-481
نویسندگان
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