View source for 3zml


==Anopheles funestus glutathione-s-transferase epsilon 2 (GSTe2) protein structure from different alelles: A single amino acid change confers high level of DDT resistance and cross resistance to permethrin in a major malaria vector in Africa==
<StructureSection load='3zml' size='340' side='right'caption='[[3zml]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zml]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_funestus Anopheles funestus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZML FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.639&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</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=3zml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zml OCA], [https://pdbe.org/3zml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zml RCSB], [https://www.ebi.ac.uk/pdbsum/3zml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zml ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G0XSZ1_ANOFN G0XSZ1_ANOFN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. RESULTS: Here, we demonstrate that the single amino acid change L119F in an up-regulated glutathione S-transferase gene, GSTe2, confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus. Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further support the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. CONCLUSIONS: This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and design suitable resistance management strategies.

A single mutation in the GSTe2 gene allows tracking of metabolically-based insecticide resistance in a major malaria vector.,Riveron JM, Yunta C, Ibrahim SS, Djouaka R, Irving H, Menze BD, Ismail HM, Hemingway J, Ranson H, Albert A, Wondji CS Genome Biol. 2014 Feb 25;15(2):R27. PMID:24565444<ref>PMID:24565444</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zml" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Anopheles funestus]]
[[Category: Large Structures]]
[[Category: Albert A]]
[[Category: Yunta C]]