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The mechanism of mio-based aminomutases in beta-amino acid biosynthesis

Academic Article
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Overview

authors

  • Christianson, C. V.
  • Montavon, T. J.
  • Festin, G. M.
  • Cooke, H. A.
  • Shen, Ben
  • Bruner, S. D.

publication date

  • December 2007

journal

  • Journal of the American Chemical Society  Journal

abstract

  • Beta-amino acids are widely used building blocks in both natural and synthetic compounds. Aromatic beta-amino acids can be biosynthesized directly from proteinogenic alpha-amino acids by the action of MIO (4-methylideneimidazole-5-one)-based aminomutase enzymes. The uncommon cofactor MIO plays a role in both ammonia lyases and 2,3-aminomutases; however, the precise mechanism of the cofactor has not been resolved. Here we provide evidence that the electrophilic cofactor uses covalent catalysis through the substrate amine to direct the elimination and subsequent readdition of ammonia. A mechanism-based inhibitor was synthesized and the X-ray cocomplex structure was determined to 2.0 A resolution. The inhibitor halts the chemistry of the reverse reaction, providing a stable complex that establishes the mode of substrate binding and the importance of tyrosine 63 in the chemistry. The proposed mechanism is consistent with the biochemistry of aminomutases and ammonia lyases and provides strong support for an amine-adduct mechanism of catalysis for this enzyme class.

subject areas

  • Amino Acids
  • Catalysis
  • Imidazoles
  • Intramolecular Transferases
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Identity

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja0762689

PubMed ID

  • 18052279
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Additional Document Info

start page

  • 15744

end page

  • 15745

volume

  • 129

issue

  • 51

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