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< | ==Crystal structure of Glutaryl-COA dehydrogenase from Burkholderia Pseudomallei with fragment 6421== | ||
<StructureSection load='3gnc' size='340' side='right'caption='[[3gnc]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3gnc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_1710b Burkholderia pseudomallei 1710b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GNC 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]] 2.15Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=QQQ:1-(1-METHYLETHYL)-1H-BENZIMIDAZOLE-2-SULFONIC+ACID'>QQQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3gnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gnc OCA], [https://pdbe.org/3gnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gnc RCSB], [https://www.ebi.ac.uk/pdbsum/3gnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gnc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q3JP94_BURP1 Q3JP94_BURP1] | |||
== 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/gn/3gnc_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=3gnc ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals. | |||
Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening.,Begley DW, Davies DR, Hartley RC, Hewitt SN, Rychel AL, Myler PJ, Van Voorhis WC, Staker BL, Stewart LJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt, 9):1060-9. Epub 2011 Aug 13. PMID:21904051<ref>PMID:21904051</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3gnc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acyl-CoA dehydrogenase 3D structures|Acyl-CoA dehydrogenase 3D structures]] | |||
*[[Glutaryl-CoA dehydrogenase|Glutaryl-CoA dehydrogenase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
[[ | [[Category: Burkholderia pseudomallei 1710b]] | ||
[[Category: Large Structures]] | |||
== | |||
< | |||
[[Category: Burkholderia pseudomallei]] | |||
[[Category: | |||
Latest revision as of 10:08, 6 September 2023
Crystal structure of Glutaryl-COA dehydrogenase from Burkholderia Pseudomallei with fragment 6421Crystal structure of Glutaryl-COA dehydrogenase from Burkholderia Pseudomallei with fragment 6421
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 PubMedGlutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals. Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening.,Begley DW, Davies DR, Hartley RC, Hewitt SN, Rychel AL, Myler PJ, Van Voorhis WC, Staker BL, Stewart LJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt, 9):1060-9. Epub 2011 Aug 13. PMID:21904051[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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