Abstract
Taurine/α-ketoglutarate dioxygenase is an important
enzyme that takes part in the cysteine catabolism process in the
human body and selectively hydroxylates taurine at the C¹-position.
Recent computational studies showed that in the gas-phase the
C²-H bond of taurine is substantially weaker than the C¹-H bond,
yet no evidence exists of 2-hydroxytaurine products. To this end, we
performed a detailed computational study on the selectivity patterns
in TauD. The calculations show that the second-coordination sphere
and the protonation states of residues play a major role in guiding
the enzyme to the right selectivity. Specifically, a single proton on an
active site histidine residue can change the regioselectivity of the
reaction through its electrostatic perturbations in the active site and
effectively changes the C¹-H and C²-H bond strengths of taurine.
This is further emphasized by many polar and hydrogen bonding
interactions of the protein cage in TauD with the substrate and the
oxidant that weaken the pro-R C¹-H bond and triggers a
chemoselective reaction process. Our large cluster models
reproduce the experimental free energy of activation excellently.
Original language | English |
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Journal | Chemistry – A European Journal |
Early online date | 30 Dec 2021 |
DOIs | |
Publication status | Published - 30 Dec 2021 |