Douglas Tsao - Regioselectivity of catechol O-methyltransferase confers enhancement of catalytic activity

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      Publication Details (including relevant citation   information):

      Tsao, D., Liu, S., and Dokholyan, N. V., Chemical Physics   Letters, 506:135-138, (2011)


      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.

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