抗癌化合物Taxol (paclitaxel)和很多其他天然C20二萜的生物合成中的第一步,，是一種“類異戊二烯”的環(huán)化，該反應(yīng)由紫杉二烯合成酶催化?，F(xiàn)在，來自太平洋紫杉的這種酶的X-射線晶體結(jié)構(gòu)已被確定,。其C-端催化區(qū)域以在I-類萜環(huán)化酶中所看到的方式結(jié)合并激發(fā)基質(zhì),，但N-端區(qū)域和第三個(gè)“插入”區(qū)域采取了一種II-類萜環(huán)化酶的折疊方式。這表明,，這種酶可能是所有萜環(huán)化酶的先祖,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09628
Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis
Mustafa K?ksal,Yinghua Jin,Robert M. Coates,Rodney Croteau& David W. Christianson
With more than 55,000 members identified so far in all forms of life, the family of terpene or terpenoid natural products represents the epitome of molecular biodiversity. A well-known and important member of this family is the polycyclic diterpenoid Taxol (paclitaxel), which promotes tubulin polymerization1 and shows remarkable efficacy in cancer chemotherapy2. The first committed step of Taxol biosynthesis in the Pacific yew (Taxus brevifolia)3 is the cyclization of the linear isoprenoid substrate geranylgeranyl diphosphate (GGPP) to form taxa-4(5),11(12)diene4, which is catalysed by taxadiene synthase5. The full-length form of this diterpene cyclase contains 862 residues, but a roughly 80-residue amino-terminal transit sequence is cleaved on maturation in plastids6. We now report the X-ray crystal structure of a truncation variant lacking the transit sequence and an additional 27 residues at the N terminus, hereafter designated TXS. Specifically, we have determined structures of TXS complexed with 13-aza-13,14-dihydrocopalyl diphosphate (1.82?? resolution) and 2-fluorogeranylgeranyl diphosphate (2.25?? resolution). The TXS structure reveals a modular assembly of three α-helical domains. The carboxy-terminal catalytic domain is a class?I terpenoid cyclase, which binds and activates substrate GGPP with a three-metal ion cluster. The N-terminal domain and a third ‘insertion’ domain together adopt the fold of a vestigial class?II terpenoid cyclase. A class?II cyclase activates the isoprenoid substrate by protonation instead of ionization, and the TXS structure reveals a definitive connection between the two distinct cyclase classes in the evolution of terpenoid biosynthesis.
