کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5916780 | 1163756 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The P2/P2Ⲡsites affect the substrate cleavage of TNF-α converting enzyme (TACE)
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
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چکیده انگلیسی
Tumor necrosis factor-alpha converting enzyme (TACE) is a proteinase that releases over eighty soluble proteins from their membrane-bound forms, and it has long been an intriguing therapeutic target in auto-immune diseases, and recently, in cancers. However, a haunting question is how TACE recognizes its substrates. In this work, we applied computational and experimental methods to study the role of the P2 site and the P2â² site of the substrate peptide in the substrate cleavage of TACE. In the computational complex model, the sidechains of these residues do not form key interactions with TACE, but experimentally, the mutations at these two positions largely affect the peptide cleavage efficiency in the enzymatic assay. We then showed that the P2/P2â² sites could affect the efficiency of the conformation search for the correct peptide orientation, which in turn affects the substrate cleavage efficiency. Our result provides new information to the better understanding of the enzymatic mechanism of TACE, and could be useful in the design of novel TACE inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 62, Issue 1, November 2014, Pages 122-128
Journal: Molecular Immunology - Volume 62, Issue 1, November 2014, Pages 122-128
نویسندگان
Sen Liu, Song Liu, Yanlin Wang, Zhaojiang Liao,