Structural and computational bases for dramatic skeletal rearrangement in anditomin biosynthesis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

3 Scopus Citations
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Author(s)

  • Yu Nakashima
  • Takaaki Mitsuhashi
  • Miki Senda
  • Hajime Sato
  • Mami Yamazaki
  • Masanobu Uchiyama
  • Toshiya Senda
  • Ikuro Abe

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)9743–9750
Journal / PublicationJournal of the American Chemical Society
Volume140
Issue number30
Early online date4 Jul 2018
Publication statusPublished - 1 Aug 2018

Abstract

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.

Citation Format(s)

Structural and computational bases for dramatic skeletal rearrangement in anditomin biosynthesis. / Nakashima, Yu; Mitsuhashi, Takaaki; Matsuda, Yudai; Senda, Miki; Sato, Hajime; Yamazaki, Mami; Uchiyama, Masanobu; Senda, Toshiya; Abe, Ikuro.

In: Journal of the American Chemical Society, Vol. 140, No. 30, 01.08.2018, p. 9743–9750.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review