کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1926235 | 1536445 | 2009 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Interaction of LDS-751 with the drug-binding site of P-glycoprotein: A Trp fluorescence steady-state and lifetime study Interaction of LDS-751 with the drug-binding site of P-glycoprotein: A Trp fluorescence steady-state and lifetime study](/preview/png/1926235.png)
P-glycoprotein (ABCB1) is an ATP-driven efflux pump which binds drugs within a large flexible binding pocket. Intrinsic Trp fluorescence was used to probe the interactions of LDS-751 (2-[4-(4-[dimethylamino]phenyl)-1,3-butadienyl]-3-ethylbenzo-thiazolium perchlorate) with purified P-glycoprotein, using steady-state/lifetime measurements and collisional quenching. The fast decay component of P-glycoprotein intrinsic fluorescence (τ1 = 0.97 ns) was unaffected by LDS-751 binding, while the slow decay component (τ2 = 4.02 ns) was quenched by dynamic and static mechanisms. Both the wavelength-dependence of the decay kinetics, and the time-resolved emission spectra, suggested the existence of excited-state relaxation processes within the protein matrix on the nanosecond time-scale, which were altered by LDS-751 binding. The fast decay component, which is more solvent-exposed, can be attributed to cytosolic/extracellular Trp residues, while the slow decay component likely arises from more buried transmembrane Trp residues. Interaction of a drug with the binding pocket of P-glycoprotein thus affects its molecular structure and fast dynamics.
Journal: Archives of Biochemistry and Biophysics - Volume 492, Issues 1–2, December 2009, Pages 17–28