View source for 2il3


==Structures of an Insect Epsilon-class Glutathione S-transferase from the Malaria Vector Anopheles Gambiae: Evidence for High DDT-detoxifying Activity==
<StructureSection load='2il3' size='340' side='right'caption='[[2il3]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2il3]] 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=2IL3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IL3 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]] 2.2&#8491;</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=2il3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2il3 OCA], [https://pdbe.org/2il3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2il3 RCSB], [https://www.ebi.ac.uk/pdbsum/2il3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2il3 ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/Q7PVS6_ANOGA Q7PVS6_ANOGA] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/il/2il3_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2il3 ConSurf].
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== Publication Abstract from PubMed ==
Glutathione S-transferases (GSTs), a major family of detoxifying enzymes, play a pivotal role in insecticide resistance in insects. In the malaria vector Anopheles gambiae, insect-specific epsilon class GSTs are associated with resistance to the organochlorine insecticide DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane]. Five of the eight class members have elevated expression levels in a DDT resistant strain. agGSTe2 is considered the most important GST in conferring DDT resistance in A. gambiae, and is the only member of the epsilon class with confirmed DDT-metabolizing activity. A delta class GST from the same species shows marginal DDT-metabolizing activity but the activity of agGSTe2 is approximately 350x higher than the delta class agGST1-6. To investigate its catalytic mechanism and the molecular basis of its unusually high DDT-metabolizing ability, three agGSTe2 crystal structures including one apo form and two binary complex forms with the co-factor glutathione (GSH) or the inhibitor S-hexylglutathione (GTX) have been solved with a resolution up to 1.4A. The structure of agGSTe2 shows the canonical GST fold with a highly conserved N-domain and a less conserved C-domain. The binding of GSH or GTX does not induce significant conformational changes in the protein. The modeling of DDT into the putative DDT-binding pocket suggests that DDT is likely to be converted to DDE [1,1-dichloro-2,2-bis-(p-chlorophenyl)ethylene] through an elimination reaction triggered by the nucleophilic attack of the thiolate group of GS(-) on the beta-hydrogen of DDT. The comparison with the less active agGST1-6 provides the structural evidence for its high DDT-detoxifying activity. In short, this is achieved through the inclination of the upper part of H4 helix (H4'' helix), which brings residues Arg112, Glu116, and Phe120 closer to the GSH-binding site resulting in a more efficient GS(-)-stabilizing hydrogen-bond-network and higher DDT-binding affinity.

Structure of an insect epsilon class glutathione S-transferase from the malaria vector Anopheles gambiae provides an explanation for the high DDT-detoxifying activity.,Wang Y, Qiu L, Ranson H, Lumjuan N, Hemingway J, Setzer WN, Meehan EJ, Chen L J Struct Biol. 2008 Nov;164(2):228-35. Epub 2008 Aug 26. PMID:18778777<ref>PMID:18778777</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Anopheles gambiae]]
[[Category: Large Structures]]
[[Category: Chen L]]
[[Category: Hemingway J]]
[[Category: Meehan EJ]]
[[Category: Ranson H]]
[[Category: Wang Y]]