کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1992264 1541075 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A three-dimensional model of CYP19 aromatase for structure-based drug design
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A three-dimensional model of CYP19 aromatase for structure-based drug design
چکیده انگلیسی

Aromatase (CYP450arom, CYP19) is an enzyme responsible for converting the aliphatic androgens androstenedione and testosterone to the aromatic estrogens estrone and estradiol, respectively. These endogenous hormones are a key factor in cancer tumor formation and proliferation through a cascade starting from estrogen binding to estrogen receptor. To interfere with the overproduction of estrogens especially in tumor tissue, it is possible to inhibit aromatase activity. This can be achieved using aromatase inhibitors. In order to design novel aromatase inhibitors, it is necessary to have an understanding of the active site of aromatase. As no crystal structure of the enzyme has yet been published, we built a homology model of aromatase using the first crystallized mammalian cytochrome enzyme, rabbit 21-progesterone hydroxylase 2C5, as a template structure. The initial model was validated with exhaustive molecular dynamics simulation with and without the natural substrate androstenedione. The resulting enzyme–substrate complex shows very good stability and only two of the residues are in disallowed regions in a Ramachandran plot.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 105, Issues 1–5, June–July 2007, Pages 63–70
نویسندگان
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