| Structural highlights
Function
[TS_CATRO] Component of iboga and aspidosperma monoterpenoid indole alkaloids (MIAs, e.g. tabersonine and catharanthine) biosynthesis pathway from 19E-geissoschizine. Catalyzes the conversion of O-acetylstemmadenine (OAS) to tabersonine, a precursor of vindoline.[1] [2]
Publication Abstract from PubMed
Cycloaddition reactions generate chemical complexity in a single step. Here we report the crystal structures of three homologous plant-derived cyclases involved in the biosynthesis of iboga and aspidosperma alkaloids. These enzymes act on the same substrate, named angryline, to generate three distinct scaffolds. Mutational analysis reveals how these highly similar enzymes control regio- and stereo-selectivity.
Structural basis of cycloaddition in biosynthesis of iboga and aspidosperma alkaloids.,Caputi L, Franke J, Bussey K, Farrow SC, Vieira IJC, Stevenson CEM, Lawson DM, O'Connor SE Nat Chem Biol. 2020 Feb 17. pii: 10.1038/s41589-019-0460-x. doi:, 10.1038/s41589-019-0460-x. PMID:32066966[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Qu Y, Easson MEAM, Simionescu R, Hajicek J, Thamm AMK, Salim V, De Luca V. Solution of the multistep pathway for assembly of corynanthean, strychnos, iboga, and aspidosperma monoterpenoid indole alkaloids from 19E-geissoschizine. Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3180-3185. doi:, 10.1073/pnas.1719979115. Epub 2018 Mar 6. PMID:29511102 doi:http://dx.doi.org/10.1073/pnas.1719979115
- ↑ Caputi L, Franke J, Farrow SC, Chung K, Payne RME, Nguyen TD, Dang TT, Soares Teto Carqueijeiro I, Koudounas K, Duge de Bernonville T, Ameyaw B, Jones DM, Vieira IJC, Courdavault V, O'Connor SE. Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. Science. 2018 Jun 15;360(6394):1235-1239. doi: 10.1126/science.aat4100. Epub 2018, May 3. PMID:29724909 doi:http://dx.doi.org/10.1126/science.aat4100
- ↑ Caputi L, Franke J, Bussey K, Farrow SC, Vieira IJC, Stevenson CEM, Lawson DM, O'Connor SE. Structural basis of cycloaddition in biosynthesis of iboga and aspidosperma alkaloids. Nat Chem Biol. 2020 Feb 17. pii: 10.1038/s41589-019-0460-x. doi:, 10.1038/s41589-019-0460-x. PMID:32066966 doi:http://dx.doi.org/10.1038/s41589-019-0460-x
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