Regioselectivity of catechol O-methyltransferase confers enhancement of catalytic activity

Douglas Tsao, Shubin Liu, Nikolay Dokholyan

Research output: Contribution to journalArticle

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Abstract

Catechol O-methyltransferase (COMT) metabolizes catechol moieties by methylating a single hydroxyl group at the meta- or para- hydroxyl position. Hydrophobic amino acids near the active site of COMT influence the regioselectivity of this reaction. Our sequence analysis highlights their importance by showing that these residues are highly conserved throughout evolution. Reaction barriers calculated in the gas phase reveal a lower barrier during methylation at the meta- position, suggesting that the observed meta-regioselectivity of COMT can be attributed to the substrate itself, and that COMT has evolved residues to orient the substrate in a manner that increases the rate of catalysis.

Original languageEnglish (US)
Pages (from-to)135-138
Number of pages4
JournalChemical Physics Letters
Volume506
Issue number4-6
DOIs
StatePublished - Apr 20 2011

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All Science Journal Classification (ASJC) codes

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

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