| Autor: |
Jacob Kronenberg, Stanley Chu, Andrew Olsen, Dustin Britton, Leif Halvorsen, Shengbo Guo, Ashwitha Lakshmi, Jason Chen, Maria Jinu Kulapurathazhe, Cetara A. Baker, Benjamin C. Wadsworth, Cynthia J. Van Acker, John G. Lehman III, Tamara C. Otto, P. Douglas Renfrew, Richard Bonneau, Jin Kim Montclare |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
ChemistryOpen, Vol 13, Iss 7, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2191-1363 |
| DOI: |
10.1002/open.202300263 |
| Popis: |
Abstract Organophosphates (OPs) are a class of neurotoxic acetylcholinesterase inhibitors including widely used pesticides as well as nerve agents such as VX and VR. Current treatment of these toxins relies on reactivating acetylcholinesterase, which remains ineffective. Enzymatic scavengers are of interest for their ability to degrade OPs systemically before they reach their target. Here we describe a library of computationally designed variants of phosphotriesterase (PTE), an enzyme that is known to break down OPs. The mutations G208D, F104A, K77A, A80V, H254G, and I274N broadly improve catalytic efficiency of VX and VR hydrolysis without impacting the structure of the enzyme. The mutation I106 A improves catalysis of VR and L271E abolishes activity, likely due to disruptions of PTE's structure. This study elucidates the importance of these residues and contributes to the design of enzymatic OP scavengers with improved efficiency. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
