2pty: Difference between revisions
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==Crystal Structure of the T. brucei enolase complexed with PEP== | |||
<StructureSection load='2pty' size='340' side='right'caption='[[2pty]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2pty]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PTY 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]] 2Å</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=PEP:PHOSPHOENOLPYRUVATE'>PEP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2pty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pty OCA], [https://pdbe.org/2pty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pty RCSB], [https://www.ebi.ac.uk/pdbsum/2pty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pty ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q38BV6_TRYB2 Q38BV6_TRYB2] | |||
== 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/pt/2pty_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=2pty ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Enolase 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<ref>PMID:17822439</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2pty" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Enolase|Enolase]] | *[[Enolase 3D structures|Enolase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Trypanosoma brucei]] | [[Category: Trypanosoma brucei]] | ||
[[Category: Dias | [[Category: Dias SMG]] | ||
[[Category: Garratt | [[Category: Garratt RC]] | ||
[[Category: Navarro | [[Category: Navarro MVAS]] | ||
[[Category: Rigden | [[Category: Rigden DJ]] | ||
Latest revision as of 14:08, 30 August 2023
Crystal Structure of the T. brucei enolase complexed with PEPCrystal Structure of the T. brucei enolase complexed with PEP
Structural highlights
FunctionEvolutionary 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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