5TYL
alpha-esterase-7 in complex with naphthalen-2-ylboronic acid
Summary for 5TYL
| Entry DOI | 10.2210/pdb5tyl/pdb |
| Related | 5TYJ 5TYK 5TYM 5TYN 5TYO 5TYP |
| Descriptor | Carboxylic ester hydrolase, naphthalen-2-ylboronic acid (3 entities in total) |
| Functional Keywords | carboxylesterase, insecticide resistance, covalent inhibitor, organophosphate, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Lucilia cuprina (Green bottle fly) |
| Total number of polymer chains | 1 |
| Total formula weight | 66560.82 |
| Authors | Correy, G.J.,Jackson, C.J. (deposition date: 2016-11-21, release date: 2017-12-06, Last modification date: 2023-10-04) |
| Primary citation | Correy, G.J.,Zaidman, D.,Harmelin, A.,Carvalho, S.,Mabbitt, P.D.,Calaora, V.,James, P.J.,Kotze, A.C.,Jackson, C.J.,London, N. Overcoming insecticide resistance through computational inhibitor design. Proc.Natl.Acad.Sci.USA, 116:21012-21021, 2019 Cited by PubMed Abstract: Insecticides allow control of agricultural pests and disease vectors and are vital for global food security and health. The evolution of resistance to insecticides, such as organophosphates (OPs), is a serious and growing concern. OP resistance often involves sequestration or hydrolysis of OPs by carboxylesterases. Inhibiting carboxylesterases could, therefore, restore the effectiveness of OPs for which resistance has evolved. Here, we use covalent virtual screening to produce nano-/picomolar boronic acid inhibitors of the carboxylesterase αE7 from the agricultural pest as well as a common Gly137Asp αE7 mutant that confers OP resistance. These inhibitors, with high selectivity against human acetylcholinesterase and low to no toxicity in human cells and in mice, act synergistically with the OPs diazinon and malathion to reduce the amount of OP required to kill by up to 16-fold and abolish resistance. The compounds exhibit broad utility in significantly potentiating another OP, chlorpyrifos, against the common pest, the peach-potato aphid (). These compounds represent a solution to OP resistance as well as to environmental concerns regarding overuse of OPs, allowing significant reduction of use without compromising efficacy. PubMed: 31575743DOI: 10.1073/pnas.1909130116 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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