Molecular binding of different classes of organophosphates to methyl parathion hydrolase from Ochrobactrum species
1
Issued Date
2023-01-01
Resource Type
ISSN
08873585
eISSN
10970134
Scopus ID
2-s2.0-85169309512
Pubmed ID
37646471
Journal Title
Proteins: Structure, Function and Bioinformatics
Rights Holder(s)
SCOPUS
Bibliographic Citation
Proteins: Structure, Function and Bioinformatics (2023)
Suggested Citation
Bhat N., Nutho B., Hanpaibool C., Hadsadee S., Vangnai A., Rungrotmongkol T. Molecular binding of different classes of organophosphates to methyl parathion hydrolase from Ochrobactrum species. Proteins: Structure, Function and Bioinformatics (2023). doi:10.1002/prot.26579 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/89591
Title
Molecular binding of different classes of organophosphates to methyl parathion hydrolase from Ochrobactrum species
Author's Affiliation
Other Contributor(s)
Abstract
Methyl parathion hydrolase (MPH) is an enzyme of the metallo-β-lactamase superfamily, which hydrolyses a wide range of organophosphates (OPs). Recently, MPH has attracted attention as a promising enzymatic bioremediator. The crystal structure of MPH enzyme shows a dimeric form, with each subunit containing a binuclear metal ion center. MPH also demonstrates metal ion-dependent selectivity patterns. The origins of these patterns remain unclear but are linked to open questions about the more general role of metal ions in functional evolution and divergence within enzyme superfamilies. We aimed to investigate and compare the binding of different OP pesticides to MPH with cobalt(II) metal ions. In this study, MPH was modeled from Ochrobactrum sp. with different OP pesticides bound, including methyl paraoxon and dichlorvos and profenofos. The docked structures for each substrate optimized by DFT calculation were selected and subjected to atomistic molecular dynamics simulations for 500 ns. It was found that alpha metal ions did not coordinate with all the pesticides. Rather, the pesticides coordinated with less buried beta metal ions. It was also observed that the coordination of beta metal ions was perturbed to accommodate the pesticides. The binding free energy calculations and structure-based pharmacophore model revealed that all the three substrates could bind well at the active site. However, profenofos exhibit a stronger binding affinity to MPH in comparison to the other two substrates. Therefore, our findings provide molecular insight on the binding of different OP pesticides which could help us design the enzyme for OP pesticides degradation.