کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584392 | 981330 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Exploring a potential palonosetron allosteric binding site in the 5-HT3 receptor
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
5-HTIC50HEKEC505-hydroxytryptamine (serotonin) - 5-hydroxytryptamine (سروتونین)Site-directed mutagenesis - mutagenesis مواجه با سایتRadioligand binding - اتصال دهنده رادیولینگAllosteric binding site - سایت پیوند آلوستریکComputational studies - مطالعات محاسباتیAffinity constant - وابستگی ثابتPalonosetron - پالونوستررونhuman embryonic kidney - کلیه جنین انسانSerotonin receptor - گیرنده سروتونین
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Palonosetron (Aloxi) is a potent second generation 5-HT3 receptor antagonist whose mechanism of action is not yet fully understood. Palonosetron acts at the 5-HT3 receptor binding site but recent computational studies indicated other possible sites of action in the extracellular domain. To test this hypothesis we mutated a series of residues in the 5-HT3A receptor subunit (Tyr73, Phe130, Ser163, and Asp165) and in the 5-HT3B receptor subunit (His73, Phe130, Glu170, and Tyr143) that were previously predicted by in silico docking studies to interact with palonosetron. Homomeric (5-HT3A) and heteromeric (5-HT3AB) receptors were then expressed in HEK293 cells to determine the potency of palonosetron using both fluorimetric and radioligand methods to test function and ligand binding, respectively. The data show that the substitutions have little or no effect on palonosetron inhibition of 5-HT-evoked responses or binding. In contrast, substitutions in the orthosteric binding site abolish palonosetron binding. Overall, the data support a binding site for palonosetron at the classic orthosteric binding pocket between two 5-HT3A receptor subunits but not at allosteric sites previously identified by in silico modelling and docking.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 23, 1 December 2013, Pages 7523-7528
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 23, 1 December 2013, Pages 7523-7528
نویسندگان
Marta Del Cadia, Francesca De Rienzo, David A. Weston, Andrew J. Thompson, Maria Cristina Menziani, Sarah C.R. Lummis,