Tarshis L C, Yan M, Poulter C D, Sacchettini J C
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461.
Biochemistry. 1994 Sep 13;33(36):10871-7. doi: 10.1021/bi00202a004.
The synthesis of farnesyl diphosphate (FPP), a key intermediate in the isoprenoid biosynthetic pathway required for the synthesis of cholesterol and in the formation of prenylated proteins, is catalyzed by the enzyme farnesyl diphosphate synthase (FPS). The crystal structure of avian recombinant FPS, the first three-dimensional structure for any prenyltransferase, was determined to 2.6-A resolution. The enzyme exhibits a novel fold composed entirely of alpha-helices joined by connecting loops. The enzyme's most prominent structural feature is the arrangement of 10 core helices around a large central cavity. Two aspartate-rich sequences that are highly conserved among the isoprenyl diphosphate synthase family of prenyltransferases, and are essential for enzymatic activity, were found on opposite walls of this cavity, with the aspartate side chains approximately 12 A apart and facing each other. The location and metal ion binding properties of these sequences suggest that the conserved aspartate residues participate in substrate binding of catalysis.
法尼基二磷酸（FPP）是胆固醇合成及异戊二烯化蛋白形成所需的类异戊二烯生物合成途径中的关键中间体，其合成由法尼基二磷酸合酶（FPS）催化。禽类重组FPS的晶体结构是首个被确定的任何异戊二烯基转移酶的三维结构，分辨率为2.6埃。该酶呈现出一种完全由通过连接环相连的α螺旋组成的新型折叠结构。该酶最显著的结构特征是围绕一个大的中央腔排列着10个核心螺旋。在异戊二烯基二磷酸合酶家族的异戊二烯基转移酶中高度保守且对酶活性至关重要的两个富含天冬氨酸的序列，位于这个腔的相对壁上，天冬氨酸侧链相距约12埃且彼此相对。这些序列的位置和金属离子结合特性表明，保守的天冬氨酸残基参与了催化的底物结合。
