Electrostatic perturbations in the substrate‐binding pocket of taurine/α‐ketoglutarate dioxygenase determine its selectivityCitation formats

Standard

Electrostatic perturbations in the substrate‐binding pocket of taurine/α‐ketoglutarate dioxygenase determine its selectivity. / Ali, Hafiz Saqib; De Visser, Samuel.

In: Chemistry – A European Journal, 30.12.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{7b17fcb7dfd547288d5ba3055f7816a1,
title = "Electrostatic perturbations in the substrate‐binding pocket of taurine/α‐ketoglutarate dioxygenase determine its selectivity",
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.",
author = "Ali, {Hafiz Saqib} and {De Visser}, Samuel",
year = "2021",
month = dec,
day = "30",
doi = "10.1002/chem.202104167",
language = "English",
journal = "Chemistry: A European Journal ",
issn = "0947-6539",
publisher = "John Wiley & Sons Ltd",

}

RIS

TY - JOUR

T1 - Electrostatic perturbations in the substrate‐binding pocket of taurine/α‐ketoglutarate dioxygenase determine its selectivity

AU - Ali, Hafiz Saqib

AU - De Visser, Samuel

PY - 2021/12/30

Y1 - 2021/12/30

N2 - 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.

AB - 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.

U2 - 10.1002/chem.202104167

DO - 10.1002/chem.202104167

M3 - Article

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

ER -