Structure, catalysis, and inhibition mechanism of prenyltransferase

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 hormone...

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Bibliographic Details
Published in:IUBMB life 2021-01, Vol.73 (1), p.40-63
Main Authors: Chang, Hsin‐Yang, Cheng, Tien‐Hsing, Wang, Andrew H.‐J.
Format: Article
Language:English
Subjects:
Animals
Carotenoids
Catalysis
Critical Review
Critical Reviews
Dimethylallyltranstransferase - antagonists & inhibitors
Dimethylallyltranstransferase - chemistry
Dimethylallyltranstransferase - metabolism
Enzyme Inhibitors - pharmacology
Enzymes
farnesyl diphosphate
Humans
Isopentenyl diphosphate
isoprenoid
Metabolic pathways
Metabolites
Natural products
prenyltransferase
Prenyltransferases
Protein Conformation
Retinoids
Squalene
Steroid hormones
terpene
Terpenes
terpenoid
Ubiquinone
Undecaprenyl pyrophosphate
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Summary: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.
ISSN:1521-6543
1521-6551
DOI:10.1002/iub.2418