High resolution crystal structure of a fluoride-inhibited organophosphate-degrading metallohydrolase

Selleck, Christopher , Guddat, Luke W., Ollis, David L., Schenk, Gerhard and Pedroso, Marcelo Monteiro (2017) High resolution crystal structure of a fluoride-inhibited organophosphate-degrading metallohydrolase. Journal of Inorganic Biochemistry, 177 287-290. doi:10.1016/j.jinorgbio.2017.06.013


Author Selleck, Christopher
Guddat, Luke W.
Ollis, David L.
Schenk, Gerhard
Pedroso, Marcelo Monteiro
Title High resolution crystal structure of a fluoride-inhibited organophosphate-degrading metallohydrolase
Journal name Journal of Inorganic Biochemistry   Check publisher's open access policy
ISSN 0162-0134
1873-3344
Publication date 2017-06-13
Sub-type Article (original research)
DOI 10.1016/j.jinorgbio.2017.06.013
Open Access Status Not yet assessed
Volume 177
Start page 287
End page 290
Total pages 4
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Subject 1303 Biochemistry
1604 Inorganic Chemistry
Abstract Metal ion-dependent, organophosphate-degrading enzymes (OP hydrolases) have received increasing attention due to their ability to degrade and thus detoxify commonly used pesticides and nerve agents such as sarin and VX. These enzymes thus garner strong potential as bioremediators. The OP hydrolase from Agrobacterium radiobacter (OpdA) is one of the most efficient members of this group of enzymes. Previous studies have indicated that the choice of the hydrolysis-initiating nucleophile may depend on the pH of the reaction, with a metal ion-bridging hydroxide being preferred at lower pH (i.e. pH ≤ 8.5), and a terminally coordinated hydroxide at higher pH (i.e. pH > 9.0). Furthermore, fluoride was shown to be a potent inhibitor of the reaction, but only at low pH. Here, the crystal structure (1.3 Å, pH 6) of OpdA in presence of fluoride is described. While the first coordination sphere in the active site displays minimal changes in the presence of fluoride, the hydrogen bonding network that connects the dimetallic metal center to the substrate binding pocket is disrupted. Thus, the structure of fluoride-inhibited OpdA demonstrates the significance of this hydrogen bond network in controlling the mechanism and function of this enzyme.
Formatted abstract
Metal ion-dependent, organophosphate-degrading enzymes (OP hydrolases) have received increasing attention due to their ability to degrade and thus detoxify commonly used pesticides and nerve agents such as sarin and VX. These enzymes thus garner strong potential as bioremediators. The OP hydrolase from Agrobacterium radiobacter (OpdA) is one of the most efficient members of this group of enzymes. Previous studies have indicated that the choice of the hydrolysis-initiating nucleophile may depend on the pH of the reaction, with a metal ion-bridging hydroxide being preferred at lower pH (i.e. pH ≤ 8.5), and a terminally coordinated hydroxide at higher pH (i.e. pH > 9.0). Furthermore, fluoride was shown to be a potent inhibitor of the reaction, but only at low pH. Here, the crystal structure (1.3 Å, pH 6) of OpdA in presence of fluoride is described. While the first coordination sphere in the active site displays minimal changes in the presence of fluoride, the hydrogen bonding network that connects the dimetallic metal center to the substrate binding pocket is disrupted. Thus, the structure of fluoride-inhibited OpdA demonstrates the significance of this hydrogen bond network in controlling the mechanism and function of this enzyme.
Keyword Binuclear metallohydrolases
Organophosphate-degrading enzymes
Fluoride inhibition
Bioremediation
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DP150104358
FT120100694
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 07 Jul 2017, 11:38:32 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences