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| | <StructureSection load='2on5' size='340' side='right'caption='[[2on5]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2on5' size='340' side='right'caption='[[2on5]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2on5]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_hookworm Human hookworm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ON5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ON5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2on5]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Necator_americanus Necator americanus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ON5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ON5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2on7|2on7]], [[1tw9|1tw9]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <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=2on5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2on5 OCA], [https://pdbe.org/2on5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2on5 RCSB], [https://www.ebi.ac.uk/pdbsum/2on5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2on5 ProSAT]</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=2on5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2on5 OCA], [https://pdbe.org/2on5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2on5 RCSB], [https://www.ebi.ac.uk/pdbsum/2on5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2on5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/D3U1A6_NECAM D3U1A6_NECAM] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human hookworm]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Asojo, O A]] | + | [[Category: Necator americanus]] |
| - | [[Category: Goud, G]] | + | [[Category: Asojo OA]] |
| - | [[Category: Homma, H]] | + | [[Category: Goud G]] |
| - | [[Category: Hotez, P J]] | + | [[Category: Homma H]] |
| - | [[Category: Ngamelue, M]] | + | [[Category: Hotez PJ]] |
| - | [[Category: Zhan, B]] | + | [[Category: Ngamelue M]] |
| - | [[Category: Gst]]
| + | [[Category: Zhan B]] |
| - | [[Category: Hookworm]]
| + | |
| - | [[Category: Necator]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
D3U1A6_NECAM
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Human hookworm infection is a major cause of anemia and malnutrition of adults and children in the developing world. As part of on-going efforts to control hookworm infection, The Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective L3 larval stages and adult stages of the parasite. Adult stage antigens include the cytosolic glutathione-S-transferases (GSTs). Nematode GSTs facilitate the inactivation and degradation of a variety of electrophilic substrates (drugs) via the nucleophilic addition of reduced glutathione. Parasite GSTs also play significant roles in multi-drug resistance and the modulation of host-immune defense mechanisms. RESULTS: The crystal structures of Na-GST-1 and Na-GST-2, two major GSTs from Necator americanus the main human hookworm parasite, have been solved at the resolution limits of 2.4 A and 1.9 A respectively. The structure of Na-GST-1 was refined to R-factor 18.9% (R-free 28.3%) while that of Na-GST-2 was refined to R-factor 17.1% (R-free 21.7%). Glutathione usurped during the fermentation process in bound in the glutathione binding site (G-site) of each monomer of Na-GST-2. Na-GST-1 is uncomplexed and its G-site is abrogated by Gln 50. These first structures of human hookworm parasite GSTs could aid the design of novel hookworm drugs. CONCLUSION: The 3-dimensional structures of Na-GST-1 and Na-GST-2 show two views of human hookworm GSTs. While the GST-complex structure of Na-GST-2 reveals a typical GST G-site that of Na-GST-1 suggests that there is some conformational flexibility required in order to bind the substrate GST. In addition, the overall binding cavities for both are larger, more open, as well as more accessible to diverse ligands than those of GSTs from organisms that have other major detoxifying mechanisms. The results from this study could aid in the design of novel drugs and vaccine antigens.
X-ray structures of Na-GST-1 and Na-GST-2 two glutathione S-transferase from the human hookworm Necator americanus.,Asojo OA, Homma K, Sedlacek M, Ngamelue M, Goud GN, Zhan B, Deumic V, Asojo O, Hotez PJ BMC Struct Biol. 2007 Jun 26;7:42. PMID:17594497[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Asojo OA, Homma K, Sedlacek M, Ngamelue M, Goud GN, Zhan B, Deumic V, Asojo O, Hotez PJ. X-ray structures of Na-GST-1 and Na-GST-2 two glutathione S-transferase from the human hookworm Necator americanus. BMC Struct Biol. 2007 Jun 26;7:42. PMID:17594497 doi:10.1186/1472-6807-7-42
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