Transketolase Activity in the Formation of the Azinomycin Azabicycle Moiety
| Autor: | Emily Rimes, Coran M. H. Watanabe, Brendan Foley, Kendall Pryor, Flor Martinez, Lauren A Washburn, Rachel P Lee |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular 0303 health sciences Stereochemistry Protein Conformation 030302 biochemistry & molecular biology Epoxide Glutamic acid Transketolase Biochemistry Pyrrolidine 03 medical and health sciences chemistry.chemical_compound Protein structure chemistry Biosynthesis Transketolase activity Moiety Humans Azabicyclo Compounds |
| Zdroj: | Biochemistry. 58(52) |
| ISSN: | 1520-4995 |
| Popis: | The biosynthesis of the azinomycins involves the conversion of glutamic acid to an aziridino[1,2-a]pyrrolidine moiety, which together with the epoxide moiety imparts anticancer activity to these agents. The mechanism of azabicycle formation is complex and involves at least 14 enzymatic steps. Previous research has identified N-acetyl-glutamate 5-semialdehyde as a key intermediate, which originates from protection of the amino terminus of glutamic acid and subsequent reduction of the γ-carboxylate. This study reports on the seminal discovery of a thiamin-dependent transketolase responsible for the formation of 2-acetamido-5,6-dihydroxy-6-oxoheptanoic acid, which accounts for the two-carbon extension needed to complete the carbon framework of the azabicycle moiety. |
| Databáze: | OpenAIRE |
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