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Molecular binding of different classes of organophosphates to methyl parathion hydrolase from Ochrobactrum species
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  • Thanyada Rungrotmongkol,
  • Nayana Bhat,
  • Bodee Nutho,
  • Chonnikan Hanpaibool,
  • Sarinya Hadsadee,
  • Alisa Vangnai
Thanyada Rungrotmongkol
Chulalongkorn University Faculty of Science

Corresponding Author:t.rungrotmongkol@gmail.com

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Nayana Bhat
Chulalongkorn University Faculty of Science
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Bodee Nutho
Mahidol University Faculty of Science
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Chonnikan Hanpaibool
Chulalongkorn University Faculty of Science
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Sarinya Hadsadee
Chulalongkorn University Faculty of Science
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Alisa Vangnai
Chulalongkorn University Faculty of Science
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Abstract

Methyl parathion hydrolase (MPH) is an enzyme of the metallo-β-lactamase superfamily, which hydrolyses a wide range of organophosphates (OP). 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 modelled from Ochrobactrum sp. with two different classes of OP pesticides bound, including phosphomonoester (methyl paraoxon and dichlorvos) and S-substituted thiophsphotriester (profenofos). The docked structures for each substrate optimized by DFT calculation was 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 bulky 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 exhibits the stronger binding affinity to MPH in comparison to other two substrates. Therefore, the ability of the in silico analysis presented here could be informative for increasing enzyme stability and activity.
07 Mar 2023Submitted to PROTEINS: Structure, Function, and Bioinformatics
08 Mar 2023Submission Checks Completed
08 Mar 2023Assigned to Editor
08 Mar 2023Review(s) Completed, Editorial Evaluation Pending
15 Mar 2023Reviewer(s) Assigned
02 May 2023Editorial Decision: Revise Major
06 Jul 20231st Revision Received
06 Jul 2023Submission Checks Completed
06 Jul 2023Assigned to Editor
06 Jul 2023Review(s) Completed, Editorial Evaluation Pending
06 Jul 2023Reviewer(s) Assigned
31 Jul 2023Editorial Decision: Accept