کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1948632 | 1054704 | 2007 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The drug binding site of human α1-acid glycoprotein: Insight from induced circular dichroism and electronic absorption spectra
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کلمات کلیدی
CHLPCRBAGPPrPMFQrHbDPDL/P - L / PUV/Vis - UV / Visβ-Barrel - β-بشکهCotton effect - اثر پنبهUltraviolet-visible - اشعه ماوراء بنفش قابل مشاهده استTrz - خارج از منزلInduced circular dichroism - دایروی دایره ای منجر شده استICD - دفیبریلاتورهای کاردیوورتر کاشتنیdipyridamole - دیپیریدامولcircular dichroism - رنگ تابی دورانیRhodamine B - رودامین بLipocalin - لیپوکالینLigand binding - لیگاند اتصالmefloquine - ملفوخینPrimaquine - پرایمکینPropranolol - پروپرانولولcarbamazepine - کاربامازپینchlorpromazine - کلرپرمازین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Human α1-acid glycoprotein (AGP) is an important drug binding plasma protein which affects pharmacokinetical properties of various therapeutic agents. For the first time, interpretation of the induced circular dichroism (ICD) spectra of drug-AGP complexes is presented yielding valuable information on the protein binding environment. ICD spectra were obtained by novel ligands of which AGP induced optical activity have never been reported (primaquine, mefloquine, propranolol, terazosin, carbamazepine, rhodamine B) and by re-investigation of ICD spectra of protein-bound drugs published earlier (chlorpromazine, dipyridamole, prazosin). Spectroscopic features of the ICD and absorption bands of drugs combined with native AGP indicated chiral non-degenerate exciton coupling between the guest chromophore and the indole ring of an adjacent tryptophan (Trp) residue. Results of additional CD experiments performed by using recombinant AGP mutants showed no changes in the ligand binding ability of W122A in sharp contrast with the W25A which was unable to induce extrinsic CD signal with either ligand. Thus, these findings unequivocally prove that, likely via Ï-Ï stacking mechanism, Trp25 is essentially involved in the AGP binding of drugs studied here as well as of related compounds. Survey of the AGP binding data published in the literature support this conclusion. Our results provide a fast and efficient spectroscopic tool to determine the inclusion of ligand molecules into the β-barrel cavity of AGP where the conserved Trp25 is located and might be useful in ligand-binding studies of other lipocalin proteins.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - General Subjects - Volume 1770, Issue 5, May 2007, Pages 797-809
Journal: Biochimica et Biophysica Acta (BBA) - General Subjects - Volume 1770, Issue 5, May 2007, Pages 797-809
نویسندگان
Ferenc Zsila, Yasunori Iwao,