Mechanistic Implications of the Deamination of TDP-4-amino-4-deoxy-d -fucose Catalyzed by the Radical SAM Enzyme DesII
| Autor: | Geng-Min Lin, Yeonjin Ko, Mark W. Ruszczycky, Hung-wen Liu |
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| Rok vydání: | 2018 |
| Předmět: |
Streptomyces venezuelae
S-Adenosylmethionine Stereochemistry Deamination 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis Fucose chemistry.chemical_compound Ammonium Compounds Thymine Nucleotides biology Nucleoside Diphosphate Sugars 010405 organic chemistry Desosamine Substrate (chemistry) Amino Sugars Nucleofuge Lyase biology.organism_classification Streptomyces 0104 chemical sciences chemistry Oxidoreductases Radical SAM |
| Zdroj: | Biochemistry. 57:3130-3133 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | DesII is a radical SAM lyase that catalyzes a deamination reaction during the biosynthesis of desosamine in Streptomyces venezuelae. Competing mechanistic hypotheses for this radical-mediated reaction are differentiated according to whether or not a 1, 2-migration takes place and the timing of proton abstraction following generation of a substrate α-hydroxyalkyl radical intermediate. In the present study, the deuterated C4-epimer of the natural substrate, TDP-4-amino-4-deoxy-d-[3-2H]fucose, was prepared and shown to be a substrate for DesII undergoing deamination alone with a specific activity that is only marginally reduced (ca. 3-fold) with respect to deamination of the natural substrate. Furthermore, pH titration of the deamination reaction implicates the presence of a hydron acceptor that facilitates catalysis but does not appear to be necessary. Based on these as well as previously reported results, a mechanism is proposed involving direct elimination of ammonium concerted with proton transfer to the nucleofuge from the adjacent α-hydroxyalkyl radical. |
| Databáze: | OpenAIRE |
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