Effects of Active-Site Modification and Quaternary Structure on the Regioselectivity of Catechol-O-Methyltransferase.

Research output: Contribution to journalArticle

  • External authors:
  • Brian Law
  • Matthew Bennett
  • Mark Thompson
  • Sarah Shepherd

Abstract

Catechol-O-methyltransferase (COMT), an important therapeutic target in the treatment of Parkinson's disease, is also being developed for biocatalytic processes, including vanillin production, although lack of regioselectivity has precluded its more widespread application. By using structural and mechanistic information, regiocomplementary COMT variants were engineered that deliver either meta- or para-methylated catechols. X-ray crystallography further revealed how the active-site residues and quaternary structure govern regioselectivity. Finally, analogues of AdoMet are accepted by the regiocomplementary COMT mutants and can be used to prepare alkylated catechols, including ethyl vanillin.

Bibliographical metadata

Original languageEnglish
Pages (from-to)2683–2687
JournalAngewandte Chemie (International ed. in English)
Volume55
Early online date21 Jan 2016
DOIs
StatePublished - 18 Feb 2016