Structure, catalysis, and inhibition mechanism of prenyltransferase
TLDR
In this review, six distinct subsets of characterized prenyltransferases are structurally and mechanistically classified, including (1) head‐to‐tail preny synthase, (2) head-to‐head pre-nyl synthases, (3) head•to‐middle pre-NLS, (4) terpenoid cycl enzyme, (5) aromatic preNyltransferase, and (6) proteinPrenylation.Abstract:
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.read more
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References
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Journal ArticleDOI
Protein prenylation: molecular mechanisms and functional consequences.
Fang L. Zhang,Patrick J. Casey +1 more
TL;DR: The emphasis in this review is on the enzymology of prenyl protein processing and the functional significance ofPrenylation in cellular events.
Journal ArticleDOI
The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants†
TL;DR: The mevalonate route to isopentenyl diphosphate and the GAP/pyruvate pathways in plants are studied to establish an understanding of isoprenoid biosynthesis and the distribution of the pathways amongst prokaryotes and phototrophic eukaryotes.
Journal ArticleDOI
Correction: Author Correction: Integrated genomic analyses of de novo pathways underlying atypical meningiomas
Akdes Serin Harmanci,Mark W. Youngblood,Victoria E. Clark,Süleyman Coşkun,Octavian Henegariu,Daniel Duran,E. Zeynep Erson-Omay,Leon D. Kaulen,Tong Ihn Lee,Brian J. Abraham,Matthias Simon,Boris Krischek,Marco Timmer,Roland Goldbrunner,S. Bulent Omay,Jacob F Baranoski,Burçin Baran,Geneive Carrión-Grant,Hanwen Bai,Ketu Mishra-Gorur,Johannes Schramm,Jennifer Moliterno,Alexander O. Vortmeyer,Kaya Bilguvar,Katsuhito Yasuno,Richard A. Young,Murat Gunel +26 more
TL;DR: This corrects the article DOI: 10.1038/ncomms14433 to indicate that the author of the paper is a doctor of medicine rather than a scientist, as previously reported.
Journal ArticleDOI
The diversity of Rab proteins in vesicle transport.
Peter Novick,Marino Zerial +1 more
TL;DR: A number of proteins, unrelated to each other, have been identified as putative Rab effectors and functional mechanisms may be highly diversified among members of the Rab family.
Journal ArticleDOI
Structural Basis for Cyclic Terpene Biosynthesis by Tobacco 5-Epi-Aristolochene Synthase
Courtney M. Starks,Kyoungwhan Back,Kyoungwhan Back,Joseph Chappell,Joseph Chappell,Joseph P. Noel,Joseph P. Noel +6 more
TL;DR: These structures reveal an unexpected enzymatic mechanism for the synthesis of the bicyclic product, 5-epi-aristolochene, and provide a basis for understanding the stereochemical selectivity displayed by other cyclases in the biosynthesis of pharmacologically important cyclic terpenes.
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