AI Article Synopsis
- Organophosphorus hydrolase (OPH) is an enzyme that breaks down harmful chemicals like pesticides and nerve agents.
- Scientists have created versions of this enzyme that work better, with one special version called H254R showing different effects on certain chemicals.
- The study showed that the way the enzyme is shaped helps it work differently, finding a new spot on the surface where certain inhibitors can bind, affecting how it breaks down harmful substances.
Article Abstract
Organophosphorus hydrolase detoxifies a broad range of organophosphate pesticides and the chemical warfare agents (CWAs) sarin and VX. Previously, rational genetic engineering produced OPH variants with 30-fold enhancements in the hydrolysis of CWA and their analogs. One interesting variant (H254R) in which the histidine at position 254 was changed to an arginine showed a 4-fold increase in the hydrolysis of demetonS (VX analog), a 14-fold decrease with paraoxon (an insecticide), and a 183-fold decrease with DFP (sarin analog). The three-dimensional structure of this enzyme at 1.9A resolution with the inhibitor, diethyl 4-methylbenzylphosphonate (EBP), revealed that the inhibitor did not bind at the active site, but bound exclusively into a well-defined surface pocket 12 A away from the active site. This structural feature was accompanied by non-competitive inhibition of paraoxon hydrolysis by EBP with H254R, in contrast to the native enzyme, which showed competitive inhibition. These parallel structure-function characteristics identify a functional, allosteric site on the surface of this enzyme.
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| http://dx.doi.org/10.1016/j.abb.2005.08.012 | DOI Listing |
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