Mechanistic Insight into the Enantioselective Degradation of Esterase QeH to ()/()-Quizalofop-Ethyl with Molecular Dynamics Simulation Using a Residue-Specific Force Field.
Yu-Meng Zhu, Gui Yao, Song Shao, Xin-Yu Liu, Jun Xu, Chun Chen, Xing-Wang Zhang, Zhuo-Ran Huang, Cheng-Zhen Xu, Long Zhang, Xiao-Min Wu
Author Information
Yu-Meng Zhu: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Gui Yao: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Song Shao: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Xin-Yu Liu: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Jun Xu: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Chun Chen: Institute of Biomedicine, Jinan University, Guangzhou 510632, China.
Xing-Wang Zhang: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Zhuo-Ran Huang: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Cheng-Zhen Xu: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Long Zhang: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China.
Xiao-Min Wu: Anhui Province Key Laboratory of Pollutant Sensitive Materials and Environmental Remediation, College of Life Sciences, Huaibei Normal University, Huaibei 235000, China. ORCID
The enantioselective mechanism of the esterase QeH against the two enantiomers of quizalofop-ethyl (QE) has been primitively studied using computational and experimental approaches. However, it is still unclear how the esterase QeH adjusts its conformation to adapt to substrate binding and promote enzymrate interactions and catalytic dynamics were reproduced by performing independent molecular dynamics (MD) runs on the QeH-()/()-QE complexes with a newly developed residue-specific force field (RSFF2C). Our results indicated that the benzene ring of the ()-QE structure can simultaneously form anion-�� and cation-�� interactions with the side-chain group of Glu328 and Arg384 in the binding cavity of the QeH-()-QE complex, resulting in ()-QE being closer to its catalytic triplet system (Ser78-Lys81-Tyr189) with the distances measured for the hydroxyl oxygen atom of the catalytic Ser78 of QeH and the carbonyl carbon atom of ()-QE of 7.39 ��, compared to the 8.87 �� for (S)-QE, whereas the ()-QE structure can only form an anion-�� interaction with the side chain of Glu328 in the QeH-()-QE complex, being less close to its catalytic site. The computational alanine scanning mutation (CAS) calculations further demonstrated that the ��-�� stacking interaction between the indole ring of Trp351 and the benzene ring of ()/()-QE contributed a lot to the binding stability of the enzyme-substrate (QeH-()/()-QE). These results facilitate the understanding of their catalytic processes and provide new theoretical guidance for the directional design of other key enzymes for the initial degradation of aryloxyphenoxypropionate (AOPP) herbicides with higher catalytic efficiencies.
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Grants
2208085MC65/the Natural Science Foundation of Anhui Province
2023AH030077/the Outstanding Youth Project of Natural Science Research in Colleges and Universities of Anhui Province
31500594/National Natural Science Foundation of China
Molecular Dynam-ics Studies on the Enantioselective Degradation of QeH to (R)/(S)-Quizalofop-ethyl/Anhui College Students' Innovation and Entrepreneurship Training Program
