5tyk

alpha-esterase-7 in complex with 3-chloro-4-[(2-fluorophenyl)methoxy]phenylborinic acid

spinqualitylabelsall models 5tyk, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tyk is a 1 chain structure with sequence from Lucilia cuprina. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.65Å Ligands: 7N4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q25252_LUCCU Publication Abstract from PubMed 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 alphaE7 from the agricultural pest Lucilia cuprina as well as a common Gly137Asp alphaE7 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 L. cuprina 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 (Myzus persicae). 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. Overcoming insecticide resistance through computational inhibitor design.,Correy GJ, Zaidman D, Harmelin A, Carvalho S, Mabbitt PD, Calaora V, James PJ, Kotze AC, Jackson CJ, London N Proc Natl Acad Sci U S A. 2019 Oct 15;116(42):21012-21021. doi:, 10.1073/pnas.1909130116. Epub 2019 Oct 1. PMID:31575743 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carboxylesterase 3D structures

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