|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5tyo' size='340' side='right'caption='[[5tyo]], [[Resolution|resolution]] 1.57Å' scene=''> | | <StructureSection load='5tyo' size='340' side='right'caption='[[5tyo]], [[Resolution|resolution]] 1.57Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tyo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Australian_sheep_blowfly Australian sheep blowfly]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TYO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TYO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tyo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lucilia_cuprina Lucilia cuprina]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TYO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7NM:[3-(benzyloxy)-4-methylphenyl]borinic+acid'>7NM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.57Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tym|5tym]], [[5tyj|5tyj]], [[5tyk|5tyk]], [[5tyl|5tyl]], [[5tyn|5tyn]], [[5typ|5typ]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7NM:[3-(benzyloxy)-4-methylphenyl]borinic+acid'>7NM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LcaE7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7375 Australian sheep blowfly])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tyo OCA], [https://pdbe.org/5tyo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tyo RCSB], [https://www.ebi.ac.uk/pdbsum/5tyo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tyo ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tyo OCA], [http://pdbe.org/5tyo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tyo RCSB], [http://www.ebi.ac.uk/pdbsum/5tyo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tyo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q25252_LUCCU Q25252_LUCCU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 26: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Australian sheep blowfly]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Correy, G J]] | + | [[Category: Lucilia cuprina]] |
| - | [[Category: Jackson, C J]] | + | [[Category: Correy GJ]] |
| - | [[Category: Carboxylesterase]] | + | [[Category: Jackson CJ]] |
| - | [[Category: Covalent inhibitor]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Insecticide resistance]]
| + | |
| - | [[Category: Organophosphate]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Correy GJ, Zaidman D, Harmelin A, Carvalho S, Mabbitt PD, Calaora V, James PJ, Kotze AC, Jackson CJ, London N. Overcoming insecticide resistance through computational inhibitor design. 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 doi:http://dx.doi.org/10.1073/pnas.1909130116
|
