QM/MM study on the O2 activation reaction of 4-hydroxylphenyl pyruvate dioxygenase reveals a common mechanism for α-ketoglutarate dependent dioxygenase

Linhui Li; Suitian Lai; Hongyan Lin; Xinyun Zhao; Xin Li; Xi Chen; Junjun Liu; Guangfu Yang; Changguo Zhan

doi:10.1016/j.cclet.2022.107803

QM/MM study on the O₂ activation reaction of 4-hydroxylphenyl pyruvate dioxygenase reveals a common mechanism for α-ketoglutarate dependent dioxygenase

Linhui Li, Suitian Lai, Hongyan Lin, Xinyun Zhao, Xin Li, Xi Chen, Junjun Liu, Guangfu Yang, Changguo Zhan

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase (HPPD) were reinvestigated by using hybrid quantum mechanics/molecular mechanics (QM/MM) approaches at the B3LYP/6-311++G(d,p):AMBER level. These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O[sbnd]O bond cleavage, where the first step was found to be rate-determining. The former step initially runs on a septet potential energy surface (PES), then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point (MECP) ^5-7M2, whereas the rest step runs on the quintet PES. The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9 kcal/mol with available experimental value of 16–17 kcal/mol. The present study challenges the widely accepted view which holds that the O₂ activation catalyzed by α-keto glutamate (α-KG) dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism of α-KG dioxygenase and/or other related Fe(II)-dependent oxygenase.

Original language	English
Article number	107803
Journal	Chinese Chemical Letters
Volume	34
Issue number	5
DOIs	https://doi.org/10.1016/j.cclet.2022.107803
State	Published - May 2023

Bibliographical note

Publisher Copyright:
© 2023

Funding

The work was supported by the National Key R&D Program (No. 2021YFD1700100 ) and National Natural Science Foundation of China (Nos. 21837001 , 21273089 ), the Open Project Fund of the Key Laboratory of the Pesticides and Chemical Biology of Central China Normal University (No. 2018-A01 ), the Fundamental Research Funds for the Central Universities, the Fundamental Research Funds for the South-Central University for Nationalities (No. CZW20020 ). We thank the high-performance computing center (HPC) platform of Huazhong University of Science and Technology and HPC of University of Kentucky for providing computing resources. The work was supported by the National Key R&D Program (No. 2021YFD1700100) and National Natural Science Foundation of China (Nos. 21837001, 21273089), the Open Project Fund of the Key Laboratory of the Pesticides and Chemical Biology of Central China Normal University (No. 2018-A01), the Fundamental Research Funds for the Central Universities, the Fundamental Research Funds for the South-Central University for Nationalities (No. CZW20020). We thank the high-performance computing center (HPC) platform of Huazhong University of Science and Technology and HPC of University of Kentucky for providing computing resources.

Funders	Funder number
Fundamental Research Funds for the South-Central University for Nationalities	CZW20020
Open Project Fund of the Key Laboratory of the Pesticides and Chemical Biology of Central China Normal University	2018-A01
University of Kentucky
National Natural Science Foundation of China (NSFC)	21837001, 21273089
National Natural Science Foundation of China (NSFC)
Huazhong University of Science and Technology
National Key Basic Research and Development Program of China	2021YFD1700100
National Key Basic Research and Development Program of China
Fundamental Research Funds for the Central Universities

Keywords

4-Hydroxylphenyl pyruvate dioxygenase
Mechanism
Minimum energy crossing point
O activation
QM/MM

ASJC Scopus subject areas

General Chemistry

Access to Document

10.1016/j.cclet.2022.107803

Cite this

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title = "QM/MM study on the O2 activation reaction of 4-hydroxylphenyl pyruvate dioxygenase reveals a common mechanism for α-ketoglutarate dependent dioxygenase",

abstract = "The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase (HPPD) were reinvestigated by using hybrid quantum mechanics/molecular mechanics (QM/MM) approaches at the B3LYP/6-311++G(d,p):AMBER level. These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O[sbnd]O bond cleavage, where the first step was found to be rate-determining. The former step initially runs on a septet potential energy surface (PES), then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point (MECP) 5-7M2, whereas the rest step runs on the quintet PES. The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9 kcal/mol with available experimental value of 16–17 kcal/mol. The present study challenges the widely accepted view which holds that the O2 activation catalyzed by α-keto glutamate (α-KG) dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism of α-KG dioxygenase and/or other related Fe(II)-dependent oxygenase.",

keywords = "4-Hydroxylphenyl pyruvate dioxygenase, Mechanism, Minimum energy crossing point, O activation, QM/MM",

author = "Linhui Li and Suitian Lai and Hongyan Lin and Xinyun Zhao and Xin Li and Xi Chen and Junjun Liu and Guangfu Yang and Changguo Zhan",

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year = "2023",

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doi = "10.1016/j.cclet.2022.107803",

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T1 - QM/MM study on the O2 activation reaction of 4-hydroxylphenyl pyruvate dioxygenase reveals a common mechanism for α-ketoglutarate dependent dioxygenase

AU - Li, Linhui

AU - Lai, Suitian

AU - Lin, Hongyan

AU - Zhao, Xinyun

AU - Li, Xin

AU - Chen, Xi

AU - Liu, Junjun

AU - Yang, Guangfu

AU - Zhan, Changguo

PY - 2023/5

Y1 - 2023/5

N2 - The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase (HPPD) were reinvestigated by using hybrid quantum mechanics/molecular mechanics (QM/MM) approaches at the B3LYP/6-311++G(d,p):AMBER level. These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O[sbnd]O bond cleavage, where the first step was found to be rate-determining. The former step initially runs on a septet potential energy surface (PES), then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point (MECP) 5-7M2, whereas the rest step runs on the quintet PES. The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9 kcal/mol with available experimental value of 16–17 kcal/mol. The present study challenges the widely accepted view which holds that the O2 activation catalyzed by α-keto glutamate (α-KG) dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism of α-KG dioxygenase and/or other related Fe(II)-dependent oxygenase.

AB - The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase (HPPD) were reinvestigated by using hybrid quantum mechanics/molecular mechanics (QM/MM) approaches at the B3LYP/6-311++G(d,p):AMBER level. These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O[sbnd]O bond cleavage, where the first step was found to be rate-determining. The former step initially runs on a septet potential energy surface (PES), then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point (MECP) 5-7M2, whereas the rest step runs on the quintet PES. The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9 kcal/mol with available experimental value of 16–17 kcal/mol. The present study challenges the widely accepted view which holds that the O2 activation catalyzed by α-keto glutamate (α-KG) dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism of α-KG dioxygenase and/or other related Fe(II)-dependent oxygenase.

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