کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10768313 | 1050806 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Selective inhibition of extracellular signal-regulated kinase (ERK) represents a potential approach for the treatment of cancer and other diseases; however, no selective inhibitors are currently available. Here, we describe an ERK-selective inhibitor, FR180204, and determine the structural basis of its selectivity. FR180204 inhibited the kinase activity of ERK1 and ERK2, with Ki values 0.31 and 0.14 μM, respectively. Lineweaver-Burk analysis of the binding interaction revealed that FR180204 acted as competitive inhibitor of ATP. In mink lung epithelial Mv1Lu cells, FR180204 inhibited TGFβ-induced luciferase-expression. X-ray crystal structure analysis of the human ERK2/FR180204 complex revealed that Q105, D106, L156, and C166, which form the ATP-binding pocket on ERK, play important roles in the drug/protein interaction. These results suggest that FR180204 is an ERK-selective and cell-permeable inhibitor, and could be useful for elucidating the roles of ERK as well as for drug development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 336, Issue 1, 14 October 2005, Pages 357-363
Journal: Biochemical and Biophysical Research Communications - Volume 336, Issue 1, 14 October 2005, Pages 357-363
نویسندگان
Makoto Ohori, Takayoshi Kinoshita, Mitsuru Okubo, Kentaro Sato, Akiko Yamazaki, Hiroyuki Arakawa, Shintaro Nishimura, Noriaki Inamura, Hidenori Nakajima, Masahiro Neya, Hiroshi Miyake, Takashi Fujii,