کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1316273 976441 2009 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Copper·Lys-Gly-His-Lys mediated cleavage of tRNAPhe: Studies of reaction mechanism and cleavage specificity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Copper·Lys-Gly-His-Lys mediated cleavage of tRNAPhe: Studies of reaction mechanism and cleavage specificity
چکیده انگلیسی

The reactivity of [Cu2+·Lys-Gly-His-Lys-NH2]2+ and [Cu2+·Lys-Gly-His-Lys]+ toward tRNAPhe has been evaluated. The amidated and carboxylate forms of the copper peptides display complex binding behavior with strong and weak sites evident (KD1app∼71μM, KD2app∼211μM for the amide form; and KD1app∼34μM, KD2app∼240μM for the carboxylate form), while Cu2+(aq) yielded KD1app∼81μM and KD2app∼136μM. The time-dependence of the reaction of [Cu2+·Lys-Gly-His-Lys]+ and [Cu2+·Lys-Gly-His-Lys-NH2]2+ with tRNAPhe yielded kobs ∼ 0.075 h−1 for both complexes. HPLC analysis of the reaction products demonstrated guanine as the sole base product. Mass spectrometric data shows a limited number of cleavage fragments with product peak masses consistent with chemistry occurring at a discrete site defined by the structurally contiguous D and TΨC loops, and in a domain where high affinity magnesium centers have previously been observed to promote hydrolysis of the tRNAPhe backbone. This cleavage pattern is more selective than that previously observed by Long and coworkers for nickel complexes of a series of C-terminally amidated peptides (Gly-Gly-His, Lys-Gly-His, and Arg-Gly-His), and may reflect variations in structural recognition and a distinct reaction path by the nickel derivatives. The data emphasizes the optimal positioning of the metal-associated reactive oxygen species, relative to scissile bonds, as a major criterion for development of efficient catalytic nucleases or therapeutics.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 103, Issue 6, June 2009, Pages 871–875
نویسندگان
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