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==LEISHMANIA MEXICANA GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IN COMPLEX WITH INHIBITORS==
==LEISHMANIA MEXICANA GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IN COMPLEX WITH INHIBITORS==
<StructureSection load='1i33' size='340' side='right' caption='[[1i33]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='1i33' size='340' side='right'caption='[[1i33]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1i33]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Leime Leime]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I33 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I33 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1i33]] is a 6 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=1I33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I33 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TND:N-1,2,3,4-TETRAHYDRONAPHTH-1-YL-2-[3,5-DIMETHOXYBENZAMIDO]-2-DEOXY-ADENOSINE'>TND</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]] 3&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gyp|1gyp]], [[1gyq|1gyq]], [[1i32|1i32]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TND:N-1,2,3,4-TETRAHYDRONAPHTH-1-YL-2-[3,5-DIMETHOXYBENZAMIDO]-2-DEOXY-ADENOSINE'>TND</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] </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=1i33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i33 OCA], [https://pdbe.org/1i33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i33 RCSB], [https://www.ebi.ac.uk/pdbsum/1i33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i33 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1i33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i33 OCA], [http://pdbe.org/1i33 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1i33 RCSB], [http://www.ebi.ac.uk/pdbsum/1i33 PDBsum]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G3PG_LEIME G3PG_LEIME]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i3/1i33_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i3/1i33_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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].
</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=1i33 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The glycolytic enzymes of trypanosomes are attractive drug targets, since the blood-stream form of Trypanosoma brucei lacks a functional citric acid cycle and is dependent solely on glycolysis for its energy requirements. Glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from the pathogenic trypanosomatids T. brucei, Trypanosoma cruzi and Leishmania mexicana are quite similar to each other, and yet have sufficient structural differences compared to the human enzyme to enable the structure-based design of compounds that selectively inhibit all three trypanosomatid enzymes but not the human homologue.Adenosine analogs with substitutions on N-6 of the adenine ring and on the 2' position of the ribose moiety were designed, synthesized and tested for inhibition. Two crystal structures of L. mexicana glyceraldehyde-3-phosphate dehydrogenase in complex with high-affinity inhibitors that also block parasite growth were solved at a resolution of 2.6 A and 3.0 A. The complexes crystallized in the same crystal form, with one and a half tetramers in the crystallographic asymmetric unit. There is clear electron density for the inhibitor in all six copies of the binding site in each of the two structures. The L. mexicana GAPDH subunit exhibits substantial structural plasticity upon binding the inhibitor. Movements of the protein backbone, in response to inhibitor binding, enlarge a cavity at the binding site to accommodate the inhibitor in a classic example of induced fit. The extensive hydrophobic interactions between the protein and the two substituents on the adenine scaffold of the inhibitor provide a plausible explanation for the high affinity of these inhibitors for trypanosomatid GAPDHs.
Conformational changes in Leishmania mexicana glyceraldehyde-3-phosphate dehydrogenase induced by designed inhibitors.,Suresh S, Bressi JC, Kennedy KJ, Verlinde CL, Gelb MH, Hol WG J Mol Biol. 2001 Jun 1;309(2):423-35. PMID:11371162<ref>PMID:11371162</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1i33" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Aldehyde dehydrogenase|Aldehyde dehydrogenase]]
*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
== References ==
*[[Glyceraldehyde-3-phosphate dehydrogenase 3D structures|Glyceraldehyde-3-phosphate dehydrogenase 3D structures]]
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Leime]]
[[Category: Large Structures]]
[[Category: Bressi, J C]]
[[Category: Leishmania mexicana]]
[[Category: Gelb, M H]]
[[Category: Bressi JC]]
[[Category: Hol, W G.J]]
[[Category: Gelb MH]]
[[Category: Kennedy, K J]]
[[Category: Hol WGJ]]
[[Category: Suresh, S]]
[[Category: Kennedy KJ]]
[[Category: Verlinde, C L.M J]]
[[Category: Suresh S]]
[[Category: Dehydrogenase]]
[[Category: Verlinde CLMJ]]
[[Category: Enzyme]]
[[Category: Oxidoreductase]]

Latest revision as of 10:32, 7 February 2024

LEISHMANIA MEXICANA GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IN COMPLEX WITH INHIBITORSLEISHMANIA MEXICANA GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IN COMPLEX WITH INHIBITORS

Structural highlights

1i33 is a 6 chain structure with sequence from Leishmania mexicana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

G3PG_LEIME

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1i33, resolution 3.00Å

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