Decomposition of 2,4-dihalophenols by dehaloperoxidase activity and spontaneous reaction with hydrogen peroxide

Aktar, Mst Sharmin; Hill, Ransom; Holbert, Wyatt; Franzen, Stefan

doi:10.1016/j.jinorgbio.2023.112473

Cited by 2 publications

(2 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…61 In the case of DBP and DCP the secondary reaction leading to hydroxylation of 2-ClQ or 2-BrQ is an order of magnitude slower and occurs in solution outside the DHP protein for both isozymes. 62 In a subsequent study of the oxidation of 2-ClQ or 2-BrQ, 62 it was observed that the apparent "peroxygenase" activity of these two substrate products was a spontaneous reaction with H 2 O 2 in which DHP A B played only an inhibitory role. This can be understood since 2-BrQ and 2-ClQ may interact with the DHP protein to decrease the accessibility to attack by H 2 O 2 in solution.…”

Section: ■ Discussionmentioning

confidence: 99%

“…An analogous reaction is observed for TCP, which is oxidized first to 2,6-dichloroquinone (DClQ) and subsequently hydroxylated in the 3-position to form 2,6-dichloro-3-hydroxyquinone . In the case of DBP and DCP the secondary reaction leading to hydroxylation of 2-ClQ or 2-BrQ is an order of magnitude slower and occurs in solution outside the DHP protein for both isozymes . In a subsequent study of the oxidation of 2-ClQ or 2-BrQ, it was observed that the apparent “peroxygenase” activity of these two substrate products was a spontaneous reaction with H 2 O 2 in which DHP A B played only an inhibitory role.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Structural Comparison of Substrate Binding Sites in Dehaloperoxidase A and B

Aktar,

de Serrano,

Ghiladi

et al. 2024

Biochemistry

Self Cite

View full text Add to dashboard Cite

Dehalperoxidase (DHP) has diverse catalytic activities depending on the substrate binding conformation, pH, and dynamics in the distal pocket above the heme. According to our hypothesis, the molecular structure of the substrate and binding orientation in DHP guide enzymatic function. Enzyme kinetic studies have shown that the catalytic activity of DHP B is significantly higher than that of DHP A despite 96% sequence homology. There are more than 30 substrate-bound structures with DHP B, each providing insight into the nature of enzymatic binding at the active site. By contrast, the only X-ray crystallographic structures of small molecules in a complex with DHP A are phenols. This study is focused on investigating substrate binding in DHP A to compare with DHP B structures. Fifteen substrates were selected that were known to bind to DHP B in the crystal to test whether soaking substrates into DHP A would yield similar structures. Five of these substrates yielded X-ray crystal structures of substratebound DHP A, namely, 2,4-dichlorophenol (1.48 Å, PDB: 8EJN), 2,4-dibromophenol (1.52 Å, PDB: 8VSK), 4-nitrophenol (2.03 Å, PDB: 8VKC), 4-nitrocatechol (1.40 Å, PDB: 8VKD), and 4-bromo-o-cresol (1.64 Å, PDB: 8VZR). For the remaining substrates that bind to DHP B, such as cresols, 5-bromoindole, benzimidazole, 4,4-biphenol, 4.4-ethylidenebisphenol, 2,4-dimethoxyphenol, and guaiacol, the electron density maps in DHP A are not sufficient to determine the presence of the substrates, much less their orientation. In our hands, only phenols, 4-Br-o-cresol, and 4-nitrocatechol can be soaked into crystalline DHP A. None of the larger substrates were observed to bind. A minimum of seven hanging drops were selected for soaking with more than 50 crystals screened for each substrate. The five high-quality examples of direct comparison of modes of binding in DHP A and B for the same substrate provide further support for the hypothesis that the substrate-binding conformation determines the enzyme function of DHP.

show abstract

Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%