Structure, catalysis, and inhibition mechanism of prenyltransferase.
Structure, catalysis, and inhibition mechanism of prenyltransferase.
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作者：
Chang HY;Cheng TH;Wang AH
类异戊二烯，也被称为萜烯或萜类，是一大类天然产物，由五碳二磷酸异戊烯基或其异构体二磷酸二甲基烯丙基组成。类异戊二烯在结构和功能上具有多样性，包括醇类、类固醇激素、类胡萝卜素、类维甲酸、芳香代谢物、泛醌类异戊二烯侧链和类异戊二烯附着的信号蛋白。类异戊二烯的生产是由一组被称为戊烯基转移酶的酶催化的，如法尼基转移酶、香叶基转移酶、萜类环化酶、角鲨烯合成酶、芳香戊烯基转移酶以及顺式和反式戊烯基转移酶。由于这些酶是细胞过程和代谢途径的关键，它们有望成为新药发现的潜在靶点。在这篇综述中，我们从结构和机制上对六种不同的戊烯基转移酶进行了分类，包括(1)头-尾戊烯基合成酶，(2)头-头戊烯基合成酶，(3)头-中间戊烯基合成酶，(4)萜类环化酶，(5)芳香戊烯基转移酶，(6)蛋白质戊烯酰化。这些酶的抑制剂对几种疾病的潜在治疗进行了讨论。最后，对整体膜酶十一戊烯基焦磷酸磷酸酶结构的最新研究结果进行了讨论。
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.
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DOI：
10.1073/pnas.96.23.13062
发表时间：
1999-11-09
影响因子：
11.1
作者：
Burke, CC;Wildung, MR;Croteau, R
通讯作者：
Croteau, R
影响因子：
16.6
作者：
Birladeanu, L
通讯作者：
Birladeanu, L
影响因子：
4.8
作者：
Chang, SY;Ko, TP;Wang, AHJ
通讯作者：
Wang, AHJ
影响因子：
2.9
作者：
Cao, Rong;Chen, Cammy K. -M.;Oldfield, Eric
通讯作者：
Oldfield, Eric
病原细菌中的头对头异戊二烯合成酶
DOI：
10.1002/cbic.201700099
发表时间：
2017-06-01
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
Schwalen CJ;Feng X;Liu W;O-Dowd B;Ko TP;Shin CJ;Guo RT;Mitchell DA;Oldfield E
通讯作者：
Oldfield E