کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1948526 | 1054699 | 2007 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Engineering the enantioselectivity of glutathione transferase by combined active-site mutations and chemical modifications
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Engineering the enantioselectivity of glutathione transferase by combined active-site mutations and chemical modifications Engineering the enantioselectivity of glutathione transferase by combined active-site mutations and chemical modifications](/preview/png/1948526.png)
چکیده انگلیسی
Based on the crystal structure of human glutathione transferase M1-1, cysteine residues were introduced in the substrate-binding site of a Cys-free mutant of the enzyme, which were subsequently alkylated with 1-iodoalkanes. By different combinations of site-specific mutations and chemical modifications of the enzyme the enantioselectivity in the conjugation of glutathione with the epoxide-containing substrates 1-phenylpropylene oxide and styrene-7,8-oxide were enhanced up to 9- and 10-fold. The results also demonstrate that the enantioselectivity can be diminished, or even reversed, by suitable modifications, which can be valuable under some conditions. The redesign of the active-site structure for enhanced or diminished enantioselectivities have divergent requirements for different epoxides, calling for a combinatorial approach involving alternative mutations and chemical modifications to optimize the enantioselectivity for a targeted substrate. This approach outlines a general method of great potential for fine-tuning substrate specificity and tailoring stereoselectivity of recombinant enzymes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - General Subjects - Volume 1770, Issue 9, September 2007, Pages 1374-1381
Journal: Biochimica et Biophysica Acta (BBA) - General Subjects - Volume 1770, Issue 9, September 2007, Pages 1374-1381
نویسندگان
Ylva Ivarsson, Malena A. Norrgård, Ulf Hellman, Bengt Mannervik,