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 journalArticlepeer-review

3 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 languageEnglish
Article number107803
JournalChinese Chemical Letters
Volume34
Issue number5
DOIs
StatePublished - May 2023

Bibliographical note

Publisher Copyright:
© 2023

Keywords

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

ASJC Scopus subject areas

  • General Chemistry

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