PMID- 37100030
OWN - NLM
STAT- MEDLINE
DCOM- 20230509
LR  - 20230605
IS  - 1549-960X (Electronic)
IS  - 1549-9596 (Linking)
VI  - 63
IP  - 9
DP  - 2023 May 8
TI  - Computational Study of the Fe(II) and alpha-Ketoglutarate-Dependent Aryloxyalkanoate 
      Dioxygenase (AAD-1) in the Degradation of the Herbicide 2,4-Dichlorophenoxyacetic 
      Acid.
PG  - 2759-2768
LID - 10.1021/acs.jcim.2c01381 [doi]
AB  - The AAD-1 enzyme belongs to the Fe(II) and alpha-ketoglutarate (Fe/alphaKG)-dependent 
      nonheme aryloxyalkanoate dioxygenase family (AADs), which catalyzes the breakdown 
      of 2,4-dichlorophenoxyacetic acid (2,4-D, an active ingredient of thousands of 
      commercial herbicides) by using the highly active Fe(IV) horizontal lineO complex. Multiple 
      species of bacteria degrade 2,4-D via a pathway initiated by AADs; however, the 
      detail of how they promote the cleavage of the ether C-O bond to generate 
      2,4-dichlorophenol (2,4-DCP) and glyoxylate is still unclear, which is the 
      prerequisite for the further degradation of these halogenated aromatics. In this 
      work, based on the crystal structure of AAD-1, the computational models were 
      constructed, and a series of QM/MM and QM-only calculations were performed to 
      explore the cleavage of the ether bond in 2,4-D with the catalysis of AAD-1. Our 
      calculations reveal that AAD-1 may be only responsible for the hydroxylation of 
      the substrate to generate the intermediate hemiacetal, which corresponds to an 
      overall energy barrier of 14.2 kcal/mol on the quintet state surface, and the 
      decomposition of the hemiacetal in the active site center of AAD-1 was calculated 
      to be rather slow, corresponding to an energy barrier of 24.5 kcal/mol. In 
      contrast, the decomposition of the free hemiacetal molecule in a solvent was 
      calculated to be quite easy. Whether the decomposition of the hemiacetal occurs 
      inside or outside the activation site is still worthy of experimental 
      verification.
FAU - Zhang, Xue
AU  - Zhang X
AD  - School of Chemistry and Chemical Engineering, Shandong University, Jinan, 
      Shandong 250100, China.
FAU - Li, Xinyi
AU  - Li X
AD  - School of Chemistry and Chemical Engineering, Shandong University, Jinan, 
      Shandong 250100, China.
FAU - Wang, Yijing
AU  - Wang Y
AD  - School of Chemistry and Chemical Engineering, Shandong University, Jinan, 
      Shandong 250100, China.
FAU - Zhang, Xianghui
AU  - Zhang X
AD  - School of Chemistry and Chemical Engineering, Shandong University, Jinan, 
      Shandong 250100, China.
FAU - Liu, Yongjun
AU  - Liu Y
AUID- ORCID: 0000-0002-1686-8272
AD  - School of Chemistry and Chemical Engineering, Shandong University, Jinan, 
      Shandong 250100, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230426
PL  - United States
TA  - J Chem Inf Model
JT  - Journal of chemical information and modeling
JID - 101230060
RN  - 0 (Herbicides)
RN  - 0 (Ketoglutaric Acids)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - 0 (Phenoxyacetates)
RN  - 2577AQ9262 (2,4-Dichlorophenoxyacetic Acid)
RN  - 0 (Ferrous Compounds)
SB  - IM
MH  - *Herbicides/metabolism
MH  - Ketoglutaric Acids/metabolism
MH  - *Dioxygenases/chemistry/metabolism
MH  - Phenoxyacetates
MH  - 2,4-Dichlorophenoxyacetic Acid/metabolism
MH  - Ferrous Compounds/chemistry
EDAT- 2023/04/27 00:42
MHDA- 2023/05/09 06:42
CRDT- 2023/04/26 18:12
PHST- 2023/05/09 06:42 [medline]
PHST- 2023/04/27 00:42 [pubmed]
PHST- 2023/04/26 18:12 [entrez]
AID - 10.1021/acs.jcim.2c01381 [doi]
PST - ppublish
SO  - J Chem Inf Model. 2023 May 8;63(9):2759-2768. doi: 10.1021/acs.jcim.2c01381. Epub 
      2023 Apr 26.