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.

金属离子依赖性有机磷酸酯降解酶（OP水解酶）由于具有降解能力，因此可以将常用的农药和神经毒药（如沙林和VX）解毒，因此受到越来越多的关注。这些酶因此具有作为生物修复剂的强大潜力。放射土壤杆菌（OpdA）的OP水解酶是这组酶中最有效的成员之一。先前的研究表明，水解引发亲核试剂的选择可能取决于反应的pH值，在较低的pH值（即pH≤8.5）下，金属离子桥联氢氧化物是优选的，而在较高的pH值下，末端配位的氢氧化物是优选的（IEpH> 9.0）。此外，氟化物被证明是该反应的有效抑制剂，但仅在低pH下才有效。这里，描述了在氟化物存在下的OpdA的晶体结构（1.3Å，pH 6）。尽管活性位点中的第一个配位球在氟化物的存在下显示出最小的变化，但将双金属金属中心连接至底物结合口袋的氢键网络却被破坏了。因此，氟化物抑制的OpdA的结构证明了这种氢键网络在控制该酶的机制和功能中的重要性。