2imi: Difference between revisions
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[[Image: | ==Structures of an Insect Epsilon-class Glutathione S-transferase from the Malaria Vector Anopheles Gambiae: Evidence for High DDT-detoxifying Activity== | ||
<StructureSection load='2imi' size='340' side='right' caption='[[2imi]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2imi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IMI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IMI FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2il3|2il3]], [[2imk|2imk]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AF316636 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7165 Anopheles gambiae])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2imi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2imi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2imi RCSB], [http://www.ebi.ac.uk/pdbsum/2imi PDBsum]</span></td></tr> | |||
<table> | |||
== 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/im/2imi_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Glutathione S-transferase|Glutathione S-transferase]] | *[[Glutathione S-transferase|Glutathione S-transferase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Anopheles gambiae]] | [[Category: Anopheles gambiae]] | ||
[[Category: Glutathione transferase]] | [[Category: Glutathione transferase]] | ||
