کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1178340 962684 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of amino acid residue 90 in bioactivity and receptor binding capacity of tumor necrosis factor mutants
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Role of amino acid residue 90 in bioactivity and receptor binding capacity of tumor necrosis factor mutants
چکیده انگلیسی

We have previously produced two bioactive lysine-deficient mutants of TNF-α (mutTNF-K90R,-K90P) and found that these mutants have bioactivity superior to wild-type TNF (wtTNF). Because these mutants contained same amino acid except for amino acid 90, it is unclear which amino acid residue is optimal for showing bioactivity. We speculated that this amino acid position was exchangeable, and this amino acid substitution enabled the creation of lysine-deficient mutants with enhanced bioactivity. Therefore, we produced mutTNF-K90R variants (mutTNF-R90X), in which R90 was replaced with other amino acids, to assay their bioactivities and investigated the importance of amino acid position 90. As a result, mutTNF-R90X that replaced R90 with lysine, arginine and proline were bioactive, while other mutants were not bioactive. Moreover, these three mutants showed bioactivity as good as or better than wtTNF. R90 replaced with lysine or arginine had especially superior binding affinities. These results suggest that the amino acid position 90 in TNF-α is important for TNF-α bioactivity and could be altered to improve its bioactivity to generate a “super-agonist”.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1774, Issue 8, August 2007, Pages 1029–1035
نویسندگان
, , , , , , , , , , , , , ,