两类脂肪酸合酶中酮酰还原酶的结构、功能和药物开发前景

STRUCTURE, FUNCTION AND DRUG DEVELOPMENT OF KETOACETYL REDUCTASE OF TWO KINDS OF FATTY ACID SYNTHASE

自然界中脂肪酸合酶(FAS)以FASⅠ和FASⅡ两种形式存在。存在于动物中的FASⅠ是由多活性中心构成的复合酶,存在于植物和细菌中的FASⅡ则是由多个独立蛋白构成的酶体系。FASⅠ和FASⅡ中催化酮酰基团还原的酶有一定同源性,酶催化动力学和酶抑制动力学的性质相似,因分子量过大,目前尚无详细的FASⅠ空间结构信息。通过比较两种类型FAS中酮酰还原酶结构与功能的异同,进一步了解FASⅠ的结构与功能。对两种不同进化程度和存在形式的同源酶进行比较研究,将有利于揭示复合酶的结构与功能,并利于寻找新型特异性蛋白抑制剂,为新药开发提供先导化合物,具有十分重要的理论意义和应用价值。

Natural Fatty Acid Synthase (FAS) exists in two different forms as FAS I and FAS II. The animal FAS I is a multifunctional enzyme consisting of seven active domains, and FAS II existing in plants and bacteria is an enzymatic system comprising seven independent proteins. FAS I and FAS II exhibit homological characters in the enzyme catalyzing ketoacyl reduction, and they show similar enzyme catalyzing and information is not clear. The goal of this project is to compare the similarity and difference between the structure and function of two kinds of ketoacyl reductase, thereby understanding the structure and function of FAS I. The comparison studies of these two homological enzymes will help to elucidate the structure and function of multifunctional enzyme and may be beneficial to exploring new-type inhibitors with specialty, which shows great theoretic meaning and practical value in exploring leading chemicals for drug development.