Turkish Journal of Chemistry

Author ORCID Identifier

YILMAZ ÖZKILIÇ: 0000-0001-8524-532X




The cofactor of a class A monooxygenase is reduced at an external location of the enzyme and is subsequently pulled back into the active site after the reduction. This observation brings the question; is there any defense mechanism of the active site of a monooxygenase against the formation of the harmful hydrogen peroxide from the reactive C(4a)-(hydro)peroxide intermediate? In this study, the barrier energies of one to three water molecule-mediated uncoupling reaction mechanisms in water exposed reaction conditions were determined. These were found to be facile barriers. Secondly, uncoupling was modeled in the active site of kynurenine 3-monooxygenase complex which was represented with 258 atoms utilizing cluster approach. Comparison of the barrier energy of the cluster model to the models that represent the water exposed conditions revealed that the enzyme does not have an inhibitory reaction site architecture as the compared barrier energies are roughly the same. The main defense mechanism of KMO against the formation of the hydrogen peroxide is deduced to be the insulation, and without this insulation, the monooxygenation would not take place as the barrier height of the hydrogen peroxide formation within the active site is almost half of that of the monooxygenation.


Hydrogen peroxide, DFT, mechanism, C(4a)-(hydro)peroxide, uncoupling, kynurenine 3-monooxygenase

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Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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