2018年8月1日
Structural and Computational Bases for Dramatic Skeletal Rearrangement in Anditomin Biosynthesis.
Journal of the American Chemical Society
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- 巻
- 140
- 号
- 30
- 開始ページ
- 9743
- 終了ページ
- 9750
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1021/jacs.8b06084
AndA, an Fe(II)/α-ketoglutarate (αKG)-dependent enzyme, is the key enzyme that constructs the unique and congested bridged-ring system of anditomin (1), by catalyzing consecutive dehydrogenation and isomerization reactions. Although we previously characterized AndA to some extent, the means by which the enzyme facilitates this drastic structural reconstruction have remained elusive. In this study, we have solved three X-ray crystal structures of AndA, in its apo form and in the complexes with Fe(II), αKG, and two substrates. The crystal structures and mutational experiments identified several key amino acid residues important for the catalysis and provided insight into how AndA controls the reaction. Furthermore, computational calculations validated the proposed reaction mechanism for the bridged-ring formation and also revealed the requirement of a series of conformational changes during the transformation.
- ID情報
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- DOI : 10.1021/jacs.8b06084
- PubMed ID : 29972643