THE METABOLIC PATHWAYS FOR HOMONAL STEROIDS APPEAR TO BE REFLECTED IN THE STEREOCHEMISTRY OF DNA

被引:8
作者
HENDRY, LB
MULDOON, TG
MAHESH, VB
机构
[1] Department of Physiology and Endocrinology CLW 3138, Medical College of Georgia, Augusta
关键词
D O I
10.1016/0960-0760(92)90106-S
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Computer graphics and energy calculations were employed to examine the relative fit of progesterone and its major biosynthetic precursors and inactive metabolites into partially unwound double stranded DNA. Progesterone was found to be the best fitting molecule; moreover, it was the only compound which exhibited full stereochemical complementarity by inserting completely between base pairs and forming optimal hydrogen bonds with both deoxyribose-phosphate backbones. Intermediates in each step of the biosynthetic and degradation pathways were progressively increasing and decreasing fits into DNA, respectively. When the fits of various possible stereoisomers were examined, the positions of functional groups manifest in the known biosynthetic precursors were found to provide the best possible fitting structures. Conversely, the positions of functional groups of known inactive metabolites provided the worst possible fitting structures. These findings coupled with previous reports showing that the specific biological function assigned to each class of steroid hormone correlates with the formation of a unique pattern of donor/acceptor linkages confirms that hormonal structures are indeed rare in their capacity to form "lock and key" complexes with DNA. Given that all possible linkages to DNA are not yet accounted for, the existence of other naturally occurring compounds with salient biological function is predicted.
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页码:659 / 670
页数:12
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