کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1933240 1050606 2009 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The critical iron–oxygen intermediate in human aromatase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The critical iron–oxygen intermediate in human aromatase
چکیده انگلیسی

Aromatase (CYP19) is the target of several therapeutics used for breast cancer treatment and catalyzes the three-step conversion of androgens to estrogens, with an unusual C–C cleavage reaction in the third step. To better understand the CYP19 reaction, the oxy-ferrous complex of CYP19 with androstenedione substrate was cryotrapped, characterized by UV–vis spectroscopy, and cryoreduced to generate the next reaction cycle intermediate. EPR analysis revealed that the initial intermediate observed following cryoreduction is the unprotonated g1 = 2.254 peroxo-ferric intermediate, which is stable up to 180 K. Upon gradual cryoannealing, the low-spin (g1 = 2.39) product complex is formed, with no evidence for accumulation of the g1 = 2.30 hydroperoxo-ferric intermediate. The relative stabilization of the peroxo-ferric heme and the lack of observed hydroperoxo-ferric heme distinguish CYP19 from other P450s, suggesting that the proton delivery pathway is more hindered in CYP19 than in most other P450s.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 387, Issue 1, 11 September 2009, Pages 169–173
نویسندگان
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