کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10771076 1050838 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The substrate specificity of SARS coronavirus 3C-like proteinase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The substrate specificity of SARS coronavirus 3C-like proteinase
چکیده انگلیسی
The 3C-like proteinase of severe acute respiratory syndrome coronavirus (SARS) has been proposed to be a key target for structural based drug design against SARS. We have designed and synthesized 34 peptide substrates and determined their hydrolysis activities. The conserved core sequence of the native cleavage site is optimized for high hydrolysis activity. Residues at position P4, P3, and P3′ are critical for substrate recognition and binding, and increment of β-sheet conformation tendency is also helpful. A comparative molecular field analysis (CoMFA) model was constructed. Based on the mutation data and CoMFA model, a multiply mutated octapeptide S24 was designed for higher activity. The experimentally determined hydrolysis activity of S24 is the highest in all designed substrates and is close to that predicted by CoMFA. These results offer helpful information for the research on the mechanism of substrate recognition of coronavirus 3C-like proteinase.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 329, Issue 3, 15 April 2005, Pages 934-940
نویسندگان
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