2ptw: Difference between revisions
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==Crystal Structure of the T. brucei enolase complexed with sulphate, identification of a metal binding site IV== | ==Crystal Structure of the T. brucei enolase complexed with sulphate, identification of a metal binding site IV== | ||
<StructureSection load='2ptw' size='340' side='right' caption='[[2ptw]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='2ptw' size='340' side='right'caption='[[2ptw]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2ptw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PTW OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[2ptw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PTW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2PTW FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1oep|1oep]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1oep|1oep]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphopyruvate_hydratase Phosphopyruvate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.11 4.2.1.11] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphopyruvate_hydratase Phosphopyruvate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.11 4.2.1.11] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2ptw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ptw OCA], [http://pdbe.org/2ptw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ptw RCSB], [http://www.ebi.ac.uk/pdbsum/2ptw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ptw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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==See Also== | ==See Also== | ||
*[[Enolase|Enolase]] | *[[Enolase 3D structures|Enolase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Phosphopyruvate hydratase]] | [[Category: Phosphopyruvate hydratase]] | ||
[[Category: Dias, S M.G]] | [[Category: Dias, S M.G]] | ||
Revision as of 09:57, 3 June 2020
Crystal Structure of the T. brucei enolase complexed with sulphate, identification of a metal binding site IVCrystal Structure of the T. brucei enolase complexed with sulphate, identification of a metal binding site IV
Structural highlights
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 PubMedEnolase is a validated drug target in Trypanosoma brucei. To better characterize its properties and guide drug design efforts, we have determined six new crystal structures of the enzyme, in various ligation states and conformations, and have carried out complementary molecular dynamics simulations. The results show a striking structural diversity of loops near the catalytic site, for which variation can be interpreted as distinct modes of conformational variability that are explored during the molecular dynamics simulations. Our results show that sulfate may, unexpectedly, induce full closure of catalytic site loops whereas, conversely, binding of inhibitor phosphonoacetohydroxamate may leave open a tunnel from the catalytic site to protein surface offering possibilities for drug development. We also present the first complex of enolase with a novel inhibitor 2-fluoro-2-phosphonoacetohydroxamate. The molecular dynamics results further encourage efforts to design irreversible species-specific inhibitors: they reveal that a parasite enzyme-specific lysine may approach the catalytic site more closely than crystal structures suggest and also cast light on the issue of accessibility of parasite enzyme-specific cysteines to chemically modifying reagents. One of the new sulfate structures contains a novel metal-binding site IV within the catalytic site cleft. Structural flexibility in Trypanosoma brucei enolase revealed by X-ray crystallography and molecular dynamics.,de A S Navarro MV, Gomes Dias SM, Mello LV, da Silva Giotto MT, Gavalda S, Blonski C, Garratt RC, Rigden DJ FEBS J. 2007 Oct;274(19):5077-89. Epub 2007 Sep 5. PMID:17822439[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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