2iyo: Difference between revisions
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==Structural characterization of a bacterial 6PDH reveals aspects of specificity, mechanism and mode of inhibition== | |||
<StructureSection load='2iyo' size='340' side='right'caption='[[2iyo]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2iyo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lactococcus_lactis Lactococcus lactis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IYO 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]] 2.4Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6PG:6-PHOSPHOGLUCONIC+ACID'>6PG</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</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=2iyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iyo OCA], [https://pdbe.org/2iyo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iyo RCSB], [https://www.ebi.ac.uk/pdbsum/2iyo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iyo ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/6PGD_LACLM 6PGD_LACLM] Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH (By similarity). | |||
== 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/iy/2iyo_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=2iyo ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Crystal structures of recombinant Lactococcus lactis 6-phosphogluconate dehydrogenase (LlPDH) in complex with substrate, cofactor, product and inhibitors have been determined. LlPDH shares significant sequence identity with the enzymes from sheep liver and the protozoan parasite Trypanosoma brucei for which structures have been reported. Comparisons indicate that the key residues in the active site are highly conserved, as are the interactions with the cofactor and the product ribulose 5-phosphate. However, there are differences in the conformation of the substrate 6-phosphogluconate which may reflect distinct states relevant to catalysis. Analysis of the complex formed with the potent inhibitor 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does indeed mimic the high-energy intermediate state that it was designed to. The analysis also identified, as a contaminant by-product of the inhibitor synthesis, 4-phospho-d-erythronamide, which binds in similar fashion. LlPDH can now serve as a model system for structure-based inhibitor design targeting the enzyme from Trypanosoma species. | |||
Crystal structures of a bacterial 6-phosphogluconate dehydrogenase reveal aspects of specificity, mechanism and mode of inhibition by analogues of high-energy reaction intermediates.,Sundaramoorthy R, Iulek J, Barrett MP, Bidet O, Ruda GF, Gilbert IH, Hunter WN FEBS J. 2007 Jan;274(1):275-86. PMID:17222187<ref>PMID:17222187</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2iyo" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[6-phosphogluconate dehydrogenase|6-phosphogluconate dehydrogenase]] | *[[6-phosphogluconate dehydrogenase 3D structures|6-phosphogluconate dehydrogenase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Lactococcus lactis]] | [[Category: Lactococcus lactis]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Hunter WN]] | ||
[[Category: | [[Category: Iulek J]] | ||
[[Category: | [[Category: Sundaramoorthy R]] | ||
Latest revision as of 17:29, 13 December 2023
Structural characterization of a bacterial 6PDH reveals aspects of specificity, mechanism and mode of inhibitionStructural characterization of a bacterial 6PDH reveals aspects of specificity, mechanism and mode of inhibition
Structural highlights
Function6PGD_LACLM Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH (By similarity). 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 PubMedCrystal structures of recombinant Lactococcus lactis 6-phosphogluconate dehydrogenase (LlPDH) in complex with substrate, cofactor, product and inhibitors have been determined. LlPDH shares significant sequence identity with the enzymes from sheep liver and the protozoan parasite Trypanosoma brucei for which structures have been reported. Comparisons indicate that the key residues in the active site are highly conserved, as are the interactions with the cofactor and the product ribulose 5-phosphate. However, there are differences in the conformation of the substrate 6-phosphogluconate which may reflect distinct states relevant to catalysis. Analysis of the complex formed with the potent inhibitor 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does indeed mimic the high-energy intermediate state that it was designed to. The analysis also identified, as a contaminant by-product of the inhibitor synthesis, 4-phospho-d-erythronamide, which binds in similar fashion. LlPDH can now serve as a model system for structure-based inhibitor design targeting the enzyme from Trypanosoma species. Crystal structures of a bacterial 6-phosphogluconate dehydrogenase reveal aspects of specificity, mechanism and mode of inhibition by analogues of high-energy reaction intermediates.,Sundaramoorthy R, Iulek J, Barrett MP, Bidet O, Ruda GF, Gilbert IH, Hunter WN FEBS J. 2007 Jan;274(1):275-86. PMID:17222187[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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