Structure and function of cis-prenyl chain elongating enzymes
Structure and function of cis-prenyl chain elongating enzymes
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DOI：
10.1002/tcr.20083
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发表时间：
2006-01-01
期刊：
影响因子：
6.6
通讯作者：
Koyama, Tanetoshi
中科院分区：
文献类型：
--
作者：
Takahashi, Seiji;Koyama, Tanetoshi
类异戊二烯的所有碳骨架，其链长从香叶基二磷酸（C-10）到天然橡胶（C-> 10，C-000）变化很大，是通过异戊烯基二磷酸与烯丙基二磷酸通过一组通常被称为“异戊二烯基转移酶”的酶的催化功能连续缩合而合成的。异戊二烯基转移酶根据产物中异戊二烯基链单元的几何形状分为两大类，反式或（E）-异戊二烯基转移酶和顺式或（Z）-异戊二烯基转移酶。从1987年起，许多编码反式异戊二烯基转移酶的基因被克隆并清楚地表征。相反，顺式异戊二烯基转移酶的结构和详细机制完全未知，直到1998年从藤黄微球菌B-P 26中鉴定出编码十一异戊二烯基二磷酸（UPP）合酶的基因。UPP合酶的一级结构和三级结构都与反式异戊二烯基转移酶的结构完全不同。从各种生物体中鉴定的顺式异戊二烯基转移酶的一级结构的多重比对揭示了五个高度保守的区域。基于晶体结构对UPP酶保守氨基酸残基进行定点突变，阐明了其基本的催化机制。此外，通过对短链、中链和长链顺式异戊烯基转移酶结构的比较，揭示了决定产物链长的重要氨基酸残基，这使我们能够了解顺式异戊烯基转移酶最终链长的调节机制。(c)2006年日本化学杂志论坛和Wiley Periodicals，Inc.
All carbon skeletons of isoprenoids, whose chain lengths vary widely from geranyl diphosphate (C-10) to natural rubber (C-> 10,C-000), are synthesized by sequential condensation of isopentenyl diphosphate with an allylic diphosphate through catalytic functions of a group of enzymes commonly called "prenyltransferases." Prenyltransferases are classified into two major groups, trans- or (E)-prenyltransferases and cis- or (Z)-prenyltransferases, according to the geometry of the prenyl chain units in the products. From the year 1987, many genes encoding trans-prenyltransferases were cloned and clearly characterized. In contrast, the structure and detailed mechanism of cis-prenyltransferase was completely unknown until the identification of a gene encoding the undecaprenyl diphosphate (UPP) synthase from Micrococcus luteus B-P 26 in 1998. Not only the primary but also the tertiary structure of the UPP synthase is quite different from that of the trans-prenyltransferases. Multiple alignment of the primary structures of cis-prenyltransferases identified from various organisms reveals five highly conserved regions. Site-directed mutagenesis of the conserved amino acid residues in UPP synthases based on the crystal structure has elucidated the basic catalytic mechanisms. Moreover, comparison of the structures of short-, medium-, and long-chain cis-prenyltransferases reveals important amino acid residues for product chain length determination, which enabled us to understand the regulation mechanism of the ultimate chain length among cis-prenyltransferases. (c) 2006 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.