Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
IUBMB Life. 2021 Jan;73(1):40-63. doi: 10.1002/iub.2418. Epub 2020 Nov 27.
Isoprenoids, also known as terpenes or terpenoids, represent a large family of natural products composed of five-carbon isopentenyl diphosphate or its isomer dimethylallyl diphosphate as the building blocks. Isoprenoids are structurally and functionally diverse and include dolichols, steroid hormones, carotenoids, retinoids, aromatic metabolites, the isoprenoid side-chain of ubiquinone, and isoprenoid attached signaling proteins. Productions of isoprenoids are catalyzed by a group of enzymes known as prenyltransferases, such as farnesyltransferases, geranylgeranyltransferases, terpenoid cyclase, squalene synthase, aromatic prenyltransferase, and cis- and trans-prenyltransferases. Because these enzymes are key in cellular processes and metabolic pathways, they are expected to be potential targets in new drug discovery. In this review, six distinct subsets of characterized prenyltransferases are structurally and mechanistically classified, including (1) head-to-tail prenyl synthase, (2) head-to-head prenyl synthase, (3) head-to-middle prenyl synthase, (4) terpenoid cyclase, (5) aromatic prenyltransferase, and (6) protein prenylation. Inhibitors of those enzymes for potential therapies against several diseases are discussed. Lastly, recent results on the structures of integral membrane enzyme, undecaprenyl pyrophosphate phosphatase, are also discussed.
异戊二烯类，也称为萜类或类萜，代表了一大类天然产物，由五碳异戊烯二磷酸或其异构二甲烯丙基二磷酸作为构建块组成。异戊二烯类在结构和功能上具有多样性，包括多萜醇、甾体激素、类胡萝卜素、视黄醇、芳香代谢物、泛醌的异戊烯侧链和异戊烯连接的信号蛋白。异戊二烯类的产生由一组称为 prenyltransferases 的酶催化，如法呢基转移酶、香叶基转移酶、萜烯环化酶、鲨烯合酶、芳香 prenyltransferase 和顺式和反式 prenyltransferases。由于这些酶是细胞过程和代谢途径中的关键酶，因此它们有望成为新药发现的潜在靶点。在这篇综述中，根据结构和机制将六种不同的已鉴定 prenyltransferases 分为六类，包括（1）从头至尾 prenyl 合酶，（2）头对头 prenyl 合酶，（3）头至中 prenyl 合酶，（4）萜烯环化酶，（5）芳香 prenyltransferase 和（6）蛋白质 prenylation。讨论了针对几种疾病的潜在治疗方法的这些酶的抑制剂。最后，还讨论了最近关于整膜酶尿嘧啶二磷酸磷酸酶结构的结果。
