Review of the molecular modelling studies of the cytochrome P-450 estrogen synthetase enzyme, aromatase.

Drug design and discovery Pub Date : 1998-10-01
S Ahmed
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Abstract

The biosynthesis of the family of female hormones, the estrogens, is mediated by the cytochrome P-450 based enzyme Aromatase (AR), an enzyme which has been the focus of extensive research for some time and has resulted in the synthesis of numerous inhibitory compounds with varying structural properties. The crystal structure of this membrane-bound enzyme has not been determined, although that of the bacterial P-450 camphor hydroxylase enzyme has, and the latter has been used for homology modelling of AR and other related enzymes. Several workers have attempted to obtain an approximate model of the active site of AR through the use of various molecular modelling techniques using inhibitors of this enzyme, as well as a combination of experiments involving active site mutagenesis of specific areas of the P-450 backbone together with molecular modelling. In this report these studies are reviewed. In summary, although the crystal structure of AR has yet to be determined, the use of molecular modelling studies has provided useful information in the design and synthesis of its inhibitors.

细胞色素P-450雌激素合成酶、芳香化酶的分子模拟研究综述。
雌性激素家族的生物合成是由基于细胞色素P-450的酶芳香化酶(AR)介导的,一段时间以来,这种酶一直是广泛研究的焦点,并导致了许多具有不同结构性质的抑制化合物的合成。尽管细菌P-450樟脑羟化酶的晶体结构已经确定,但这种膜结合酶的晶体结构尚未确定,后者已被用于AR和其他相关酶的同源性建模。一些工作者试图通过使用这种酶的抑制剂使用各种分子建模技术,以及将P-450骨干的特定区域的活性位点诱变与分子建模相结合的实验,获得AR活性位点的近似模型。本报告对这些研究进行综述。综上所述,虽然AR的晶体结构尚未确定,但分子模拟研究的使用为其抑制剂的设计和合成提供了有用的信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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