Computational Exploration of Minimum Energy Reaction Pathway of N<sub>2</sub>O Formation from Intermediate <i>I</i> of P450nor Using an Active Center Model
P450nor is a heme-containing enzyme that catalyzes the conversion of nitric oxide (NO) to nitrous oxide (N<sub>2</sub>O). Its catalytic mechanism has attracted attention in chemistry, biology, and environmental engineering. The catalytic cycle of P450nor is proposed to consist of three m...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/24/17172 |
| Summary: | P450nor is a heme-containing enzyme that catalyzes the conversion of nitric oxide (NO) to nitrous oxide (N<sub>2</sub>O). Its catalytic mechanism has attracted attention in chemistry, biology, and environmental engineering. The catalytic cycle of P450nor is proposed to consist of three major steps. The reaction mechanism for the last step, N<sub>2</sub>O generation, remains unknown. In this study, the reaction pathway of the N<sub>2</sub>O generation from the intermediate <i>I</i> was explored with the B3LYP calculations using an active center model after the examination of the validity of the model. In the validation, we compared the heme distortions between P450nor and other oxidoreductases, suggesting a small effect of protein environment on the N<sub>2</sub>O generation reaction in P450nor. We then evaluated the electrostatic environment effect of P450nor on the hydride affinity to the active site with quantum mechanics/molecular mechanics (QM/MM) calculations, confirming that the affinity was unchanged with or without the protein environment. The active center model for P450nor showed that the N<sub>2</sub>O generation process in the enzymatic reaction undergoes a reasonable barrier height without protein environment. Consequently, our findings strongly suggest that the N<sub>2</sub>O generation reaction from the intermediate <i>I</i> depends sorely on the intrinsic reactivity of the heme cofactor bound on cysteine residue. |
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| ISSN: | 1661-6596 1422-0067 |