2y62: Difference between revisions
New page: '''Unreleased structure''' The entry 2y62 is ON HOLD Authors: Venkatesan, R., Alahuhta, M., Pihko, P.M., Wierenga, R.K. Description: Crystal structure of Leishmanial E65Q-TIM complexed... |
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The | ==Crystal structure of Leishmanial E65Q-TIM complexed with R-Glycidol phosphate== | ||
<StructureSection load='2y62' size='340' side='right'caption='[[2y62]], [[Resolution|resolution]] 1.08Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2y62]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y62 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]] 1.08Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1GP:SN-GLYCEROL-1-PHOSPHATE'>1GP</scene>, <scene name='pdbligand=G3P:SN-GLYCEROL-3-PHOSPHATE'>G3P</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2y62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y62 OCA], [https://pdbe.org/2y62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y62 RCSB], [https://www.ebi.ac.uk/pdbsum/2y62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y62 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TPIS_LEIME TPIS_LEIME] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The key residue of the active site of triosephosphate isomerase (TIM) is the catalytic glutamate, which is proposed to be important (i) as a catalytic base, for initiating the reaction, as well as (ii) for the subsequent proton shuttling steps. The structural properties of this glutamate in the liganded complex have been investigated by studying the high resolution crystal structures of typanosomal TIM, complexed with three suicide inhibitors: (S)-glycidol phosphate ((S)-GOP, at 0.99 A resolution), (R)-glycidol phosphate, ((R)-GOP, at 1.08 A resolution), and bromohydroxyacetone phosphate (BHAP, at 1.97 A resolution). The structures show that in the (S)-GOP active site this catalytic glutamate is in the well characterized, competent conformation. However, an unusual side chain conformation is observed in the (R)-GOP and BHAP complexes. In addition, Glu97, salt bridged to the catalytic lysine in the competent active site, adopts an unusual side chain conformation in these two latter complexes. The higher chemical reactivity of (S)-GOP compared with (R)-GOP, as known from solution studies, can be understood: the structures indicate that in the case of (S)-GOP, Glu167 can attack the terminal carbon of the epoxide in a stereoelectronically favored, nearly linear OCO arrangement, but this is not possible for the (R)-GOP isomer. These structures confirm the previously proposed conformational flexibility of the catalytic glutamate in its closed, liganded state. The importance of this conformational flexibility for the proton shuttling steps in the TIM catalytic cycle, which is apparently achieved by a sliding motion of the side chain carboxylate group above the enediolate plane, is also discussed. | |||
High resolution crystal structures of triosephosphate isomerase complexed with its suicide inhibitors: The conformational flexibility of the catalytic glutamate in its closed, liganded active site.,Venkatesan R, Alahuhta M, Pihko PM, Wierenga RK Protein Sci. 2011 Jun 1. doi: 10.1002/pro.667. PMID:21633986<ref>PMID:21633986</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2y62" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Triose phosphate isomerase 3D structures|Triose phosphate isomerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Leishmania mexicana]] | |||
[[Category: Alahuhta M]] | |||
[[Category: Pihko PM]] | |||
[[Category: Venkatesan R]] | |||
[[Category: Wierenga RK]] | |||
Latest revision as of 11:08, 23 August 2023
Crystal structure of Leishmanial E65Q-TIM complexed with R-Glycidol phosphateCrystal structure of Leishmanial E65Q-TIM complexed with R-Glycidol phosphate
Structural highlights
FunctionPublication Abstract from PubMedThe key residue of the active site of triosephosphate isomerase (TIM) is the catalytic glutamate, which is proposed to be important (i) as a catalytic base, for initiating the reaction, as well as (ii) for the subsequent proton shuttling steps. The structural properties of this glutamate in the liganded complex have been investigated by studying the high resolution crystal structures of typanosomal TIM, complexed with three suicide inhibitors: (S)-glycidol phosphate ((S)-GOP, at 0.99 A resolution), (R)-glycidol phosphate, ((R)-GOP, at 1.08 A resolution), and bromohydroxyacetone phosphate (BHAP, at 1.97 A resolution). The structures show that in the (S)-GOP active site this catalytic glutamate is in the well characterized, competent conformation. However, an unusual side chain conformation is observed in the (R)-GOP and BHAP complexes. In addition, Glu97, salt bridged to the catalytic lysine in the competent active site, adopts an unusual side chain conformation in these two latter complexes. The higher chemical reactivity of (S)-GOP compared with (R)-GOP, as known from solution studies, can be understood: the structures indicate that in the case of (S)-GOP, Glu167 can attack the terminal carbon of the epoxide in a stereoelectronically favored, nearly linear OCO arrangement, but this is not possible for the (R)-GOP isomer. These structures confirm the previously proposed conformational flexibility of the catalytic glutamate in its closed, liganded state. The importance of this conformational flexibility for the proton shuttling steps in the TIM catalytic cycle, which is apparently achieved by a sliding motion of the side chain carboxylate group above the enediolate plane, is also discussed. High resolution crystal structures of triosephosphate isomerase complexed with its suicide inhibitors: The conformational flexibility of the catalytic glutamate in its closed, liganded active site.,Venkatesan R, Alahuhta M, Pihko PM, Wierenga RK Protein Sci. 2011 Jun 1. doi: 10.1002/pro.667. PMID:21633986[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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