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| | ==Culex quinquefasciatus carboxylesterase B2== | | ==Culex quinquefasciatus carboxylesterase B2== |
| - | <StructureSection load='5w1u' size='340' side='right' caption='[[5w1u]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='5w1u' size='340' side='right'caption='[[5w1u]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w1u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Culqu Culqu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W1U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w1u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Culex_quinquefasciatus Culex quinquefasciatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W1U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W1U FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 2.5Å</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=5w1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1u OCA], [http://pdbe.org/5w1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w1u RCSB], [http://www.ebi.ac.uk/pdbsum/5w1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1u ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></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=5w1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w1u OCA], [https://pdbe.org/5w1u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w1u RCSB], [https://www.ebi.ac.uk/pdbsum/5w1u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w1u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q23734_CULQU Q23734_CULQU] |
| - | Carboxylesterase (CBE)-mediated metabolic resistance to organophosphate and carbamate insecticides is a major problem for the control of insect disease vectors, such as the mosquito. The most common mechanism involves overexpression of CBEs that bind to the insecticide with high affinity, thereby sequestering them before they can interact with their target. However, the absence of any structure for an insecticide-sequestering CBE limits our understanding of the molecular basis for this process. We present the first structure of a CBE involved in sequestration, Cqestbeta2(1), from the mosquito disease vector Culex quinquefasciatus. Lysine methylation was used to obtain the crystal structure of Cqestbeta2(1), which adopts a canonical alpha/beta-hydrolase fold that has high similarity to the target of organophosphate and carbamate insecticides, acetylcholinesterase. Sequence similarity networks of the insect carboxyl/cholinesterase family demonstrate that CBEs associated with metabolic insecticide resistance across many species share a level of similarity that distinguishes them from a variety of other classes. This is further emphasized by the structural similarities and differences in the binding pocket and active site residues of Cqestbeta2(1) and other insect carboxyl/cholinesterases. Stopped-flow and steady-state inhibition studies support a major role for Cqestbeta2(1) in organophosphate resistance and a minor role in carbamate resistance. Comparison with another isoform associated with insecticide resistance, Cqestbeta1, showed both enzymes have similar affinity to insecticides, despite 16 amino acid differences between the two proteins. This provides a molecular understanding of pesticide sequestration by insect CBEs and could facilitate the design of CBE-specific inhibitors to circumvent this resistance mechanism in the future.
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| - | Structure of an Insecticide Sequestering Carboxylesterase from the Disease Vector Culex quinquefasciatus: What Makes an Enzyme a Good Insecticide Sponge?,Hopkins DH, Fraser NJ, Mabbitt PD, Carr PD, Oakeshott JG, Jackson CJ Biochemistry. 2017 Oct 17;56(41):5512-5525. doi: 10.1021/acs.biochem.7b00774., Epub 2017 Sep 29. PMID:28929747<ref>PMID:28929747</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5w1u" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Culqu]] | + | [[Category: Culex quinquefasciatus]] |
| - | [[Category: Hopkins, D H]] | + | [[Category: Large Structures]] |
| - | [[Category: Jackson, C J]] | + | [[Category: Hopkins DH]] |
| - | [[Category: Alpha/beta hydrolase]] | + | [[Category: Jackson CJ]] |
| - | [[Category: Carboxylesterase]]
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| - | [[Category: Hydrolase]]
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