The UbiX flavin prenyltransferase reaction mechanism resembles class I terpene cyclase chemistry
| Autor: | Karl A. P. Payne, Arune Balaikaite, Karl Fisher, Stephen A. Marshall, A. Ni Cheallaigh, White, Stephen E. J. Rigby, David Leys |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Carboxy-Lyases Dinitrocresols Stereochemistry Decarboxylation Science Prenyltransferase General Physics and Astronomy 02 engineering and technology Flavin group Pyrophosphate Cyclase Article General Biochemistry Genetics and Molecular Biology Cofactor Fungal Proteins 03 medical and health sciences chemistry.chemical_compound Manchester Institute of Biotechnology Moiety lcsh:Science X-ray crystallography Prenylation Natural products Binding Sites Multidisciplinary biology Terpenes Leaving group General Chemistry Dimethylallyltranstransferase 021001 nanoscience & nanotechnology ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology Diphosphates 030104 developmental biology chemistry Enzyme mechanisms Biocatalysis biology.protein lcsh:Q Aspergillus niger 0210 nano-technology |
| Zdroj: | Nature Communications Marshall, S, Payne, K, Fisher, K, White, M, Ni Cheallaigh, A, Balaikaite, A, Rigby, S & Leys, D 2019, ' The UbiX flavin prenyltransferase reaction mechanism resembles Class I terpene cyclase chemistry ', Nature Communications . https://doi.org/10.1038/s41467-019-10220-1 Nature Communications, Vol 10, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-10220-1 |
| Popis: | The UbiX-UbiD enzymes are widespread in microbes, acting in concert to decarboxylate alpha-beta unsaturated carboxylic acids using a highly modified flavin cofactor, prenylated FMN (prFMN). UbiX serves as the flavin prenyltransferase, extending the isoalloxazine ring system with a fourth non-aromatic ring, derived from sequential linkage between a dimethylallyl moiety and the FMN N5 and C6. Using structure determination and solution studies of both dimethylallyl monophosphate (DMAP) and dimethyallyl pyrophosphate (DMAPP) dependent UbiX enzymes, we reveal the first step, N5-C1’ bond formation, is contingent on the presence of a dimethylallyl substrate moiety. Hence, an SN1 mechanism similar to other prenyltransferases is proposed. Selected variants of the (pyro)phosphate binding site are unable to catalyse subsequent Friedel-Crafts alkylation of the flavin C6, but can be rescued by addition of (pyro)phosphate. Thus, retention of the (pyro)phosphate leaving group is required for C6-C3’ bond formation, resembling pyrophosphate initiated class I terpene cyclase reaction chemistry. The UbiD-UbiX decarboxylase system is required for the biosynthesis of quinone cofactors. Here, the authors combine structural and biochemical analyses to elucidate the UbiX reaction mechanism, showing that it resembles the mode of action of class I terpene cyclases. |
| Databáze: | OpenAIRE |
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