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| | <StructureSection load='6arx' size='340' side='right'caption='[[6arx]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='6arx' size='340' side='right'caption='[[6arx]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6arx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Anoga Anoga]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ARX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ARX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6arx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ARX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ARX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.302Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ace, ACE1, ACHE1, AGAP001356 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7165 ANOGA])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </span></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=6arx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6arx OCA], [https://pdbe.org/6arx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6arx RCSB], [https://www.ebi.ac.uk/pdbsum/6arx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6arx ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6arx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6arx OCA], [http://pdbe.org/6arx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6arx RCSB], [http://www.ebi.ac.uk/pdbsum/6arx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6arx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACES_ANOGA ACES_ANOGA]] Rapidly hydrolyzes choline released into the synapse. | + | [https://www.uniprot.org/uniprot/ACES_ANOGA ACES_ANOGA] Rapidly hydrolyzes choline released into the synapse. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acetylcholinesterase]] | + | [[Category: Anopheles gambiae]] |
| - | [[Category: Anoga]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carlier, P R]] | + | [[Category: Carlier PR]] |
| - | [[Category: Cheung, J]] | + | [[Category: Cheung J]] |
| - | [[Category: Kalathur, R]] | + | [[Category: Kalathur R]] |
| - | [[Category: Lixuan, L]] | + | [[Category: Lixuan L]] |
| - | [[Category: Mahmood, A]] | + | [[Category: Mahmood A]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
Function
ACES_ANOGA Rapidly hydrolyzes choline released into the synapse.
Publication Abstract from PubMed
Malaria is a devastating disease in sub-Saharan Africa and is transmitted by the mosquito Anopheles gambiae. While indoor residual spraying of anticholinesterase insecticides has been useful in controlling the spread of malaria, widespread application of these compounds has led to the rise of an insecticide-resistant mosquito strain that harbors a G119S mutation in the nervous system target enzyme acetylcholinesterase. We demonstrate the atomic basis of insecticide resistance through structure determination of the G119S mutant acetylcholinesterase of An. gambiae in the ligand-free state and bound to a potent difluoromethyl ketone inhibitor. These structures reveal specific features within the active-site gorge distinct from human acetylcholinesterase, including an open channel at the base of the gorge, and provide a means for improving species selectivity in the rational design of improved insecticides for malaria vector control.
Structure of the G119S Mutant Acetylcholinesterase of the Malaria Vector Anopheles gambiae Reveals Basis of Insecticide Resistance.,Cheung J, Mahmood A, Kalathur R, Liu L, Carlier PR Structure. 2018 Jan 2;26(1):130-136.e2. doi: 10.1016/j.str.2017.11.021. Epub 2017, Dec 21. PMID:29276037[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cheung J, Mahmood A, Kalathur R, Liu L, Carlier PR. Structure of the G119S Mutant Acetylcholinesterase of the Malaria Vector Anopheles gambiae Reveals Basis of Insecticide Resistance. Structure. 2018 Jan 2;26(1):130-136.e2. doi: 10.1016/j.str.2017.11.021. Epub 2017, Dec 21. PMID:29276037 doi:http://dx.doi.org/10.1016/j.str.2017.11.021
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