4edf - Revision history

OCA at 14:58, 14 March 2024

OCA — Thu, 14 Mar 2024 14:58:17 GMT

←Older revision		Revision as of 14:58, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EDF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EDF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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]] 2.08Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [https://pdbe.org/4edf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [https://www.ebi.ac.uk/pdbsum/4edf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4edf ProSAT]</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [https://pdbe.org/4edf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [https://www.ebi.ac.uk/pdbsum/4edf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4edf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.	+	[https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Human UDP-alpha-d-glucose dehydrogenase (hUGDH) catalyzes the NAD(+)-dependent oxidation of UDP-alpha-d-glucose (UDG) to produce UDP-alpha-d-glucuronic acid. The oligomeric structure of hUGDH is dynamic and can form two distinct hexameric complexes in solution. The active form of hUGDH consists of dimers that undergo a concentration-dependent association to form a hexamer with 32 symmetry. In the presence of the allosteric feedback inhibitor UDP-alpha-d-xylose (UDX), hUGDH changes shape to form an inactive, horseshoe-shaped complex. Previous studies have identified the UDX-induced allosteric mechanism that changes the hexameric structure to inhibit the enzyme. Here, we investigate the role of the 32 symmetry hexamer in the catalytic cycle. We engineered a stable hUGDH dimer by introducing a charge-switch substitution (K94E) in the hexamer-building interface (hUGDH(K94E)). The k(cat) of hUGDH(K94E) is approximately 160-fold lower than that of the wild-type enzyme, suggesting that the hexamer is the catalytically relevant state. We also show that cofactor binding triggers the formation of the 32 symmetry hexamer, but UDG is needed for the stability of the complex. The hUGDH(K94E) crystal structure at 2.08 A resolution identifies loop(88-110) as the cofactor-responsive allosteric switch that drives hexamer formation; loop(88-110) directly links cofactor binding to the stability of the hexamer-building interface. In the interface, loop(88-110) packs against the Thr131-loop/alpha6 helix, the allosteric switch that responds to the feedback inhibitor UDX. We also identify a structural element (the S-loop) that explains the indirect stabilization of the hexamer by substrate and supports a sequential, ordered binding of the substrate and cofactor. These observations support a model in which (i) UDG binds to the dimer and stabilizes the S-loop to promote cofactor binding and (ii) cofactor binding orders loop(88-110) to induce formation of the catalytically active hexamer.	+
-		+
-	Cofactor Binding Triggers a Molecular Switch To Allosterically Activate Human UDP-alpha-d-glucose 6-Dehydrogenase.,Sennett NC, Kadirvelraj R, Wood ZA Biochemistry. 2012 Nov 20;51(46):9364-74. doi: 10.1021/bi301067w. Epub 2012 Nov, 8. PMID:23106432<ref>PMID:23106432</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4edf" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:05, 28 September 2022

OCA — Wed, 28 Sep 2022 07:05:49 GMT

←Older revision		Revision as of 07:05, 28 September 2022
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	==Dimeric hUGDH, K94E==		==Dimeric hUGDH, K94E==
-	<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>	+	<StructureSection load='4edf' size='340' side='right'caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EDF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EDF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q3e\|2q3e]], [[2qg4\|2qg4]], [[3prj\|3prj]], [[3ptz\|3ptz]], [[3tf5\|3tf5]]</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [https://pdbe.org/4edf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [https://www.ebi.ac.uk/pdbsum/4edf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4edf ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Gene ID. 7358, UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [~~http~~://pdbe.org/4edf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4edf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4edf ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.	+	[[https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~UDP-glucose 6-dehydrogenase~~]]	+	[[Category: Large Structures]]
-	[[Category: Sennett~~, N C~~]]	+	[[Category: Sennett NC]]
-	[[Category: Wood~~, Z A]]~~	+	[[Category: Wood ZA]]
-	~~[[Category: Glucuronidation]]~~	+
-	~~[[Category: Mdr]]~~	+
-	~~[[Category: Medium chain dehydrogenase]]~~	+
-	~~[[Category: Molecular switch]]~~	+
-	~~[[Category: Oligomeric state]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Rossmann fold~~]]	+

OCA at 17:49, 5 August 2016

OCA — Fri, 05 Aug 2016 17:49:51 GMT

←Older revision		Revision as of 17:49, 5 August 2016
Line 1:		Line 1:
		+
	==Dimeric hUGDH, K94E==		==Dimeric hUGDH, K94E==
	<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Gene ID. 7358, UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Gene ID. 7358, UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [http://www.ebi.ac.uk/pdbsum/4edf PDBsum]</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [http://pdbe.org/4edf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [http://www.ebi.ac.uk/pdbsum/4edf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4edf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4edf" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 04:35, 25 December 2014

OCA — Thu, 25 Dec 2014 04:35:01 GMT

←Older revision		Revision as of 04:35, 25 December 2014
Line 2:		Line 2:
	<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EDF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EDF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q3e\|2q3e]], [[2qg4\|2qg4]], [[3prj\|3prj]], [[3ptz\|3ptz]], [[3tf5\|3tf5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q3e\|2q3e]], [[2qg4\|2qg4]], [[3prj\|3prj]], [[3ptz\|3ptz]], [[3tf5\|3tf5]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Gene ID. 7358, UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [http://www.ebi.ac.uk/pdbsum/4edf PDBsum]</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [http://www.ebi.ac.uk/pdbsum/4edf PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: UDP-glucose 6-dehydrogenase]]		[[Category: UDP-glucose 6-dehydrogenase]]
	[[Category: Sennett, N C]]		[[Category: Sennett, N C]]

OCA at 07:33, 12 November 2014

OCA — Wed, 12 Nov 2014 07:33:59 GMT

←Older revision		Revision as of 07:33, 12 November 2014
Line 2:		Line 2:
	<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>		<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EDF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EDF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q3e\|2q3e]], [[2qg4\|2qg4]], [[3prj\|3prj]], [[3ptz\|3ptz]], [[3tf5\|3tf5]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q3e\|2q3e]], [[2qg4\|2qg4]], [[3prj\|3prj]], [[3ptz\|3ptz]], [[3tf5\|3tf5]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Gene ID. 7358, UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [http://www.ebi.ac.uk/pdbsum/4edf PDBsum]</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [http://www.ebi.ac.uk/pdbsum/4edf PDBsum]</span></td></tr>
Line 21:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Homo sapiens]]
	[[Category: UDP-glucose 6-dehydrogenase]]		[[Category: UDP-glucose 6-dehydrogenase]]
-	[[Category: Sennett, N C.]]	+	[[Category: Sennett, N C]]
-	[[Category: Wood, Z A.]]	+	[[Category: Wood, Z A]]
	[[Category: Glucuronidation]]		[[Category: Glucuronidation]]
	[[Category: Mdr]]		[[Category: Mdr]]

OCA at 14:07, 3 November 2014

OCA — Mon, 03 Nov 2014 14:07:10 GMT

←Older revision		Revision as of 14:07, 3 November 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4edf~~\| ~~PDB~~=4edf \| ~~SCENE~~= }}	+	==Dimeric hUGDH, K94E==
-	===~~Dimeric hUGDH~~, ~~K94E~~===	+	<StructureSection load='4edf' size='340' side='right' caption='[[4edf]], [[Resolution\|resolution]] 2.08Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23106432}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4edf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EDF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q3e\|2q3e]], [[2qg4\|2qg4]], [[3prj\|3prj]], [[3ptz\|3ptz]], [[3tf5\|3tf5]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Gene ID. 7358, UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [http://www.ebi.ac.uk/pdbsum/4edf PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human UDP-alpha-d-glucose dehydrogenase (hUGDH) catalyzes the NAD(+)-dependent oxidation of UDP-alpha-d-glucose (UDG) to produce UDP-alpha-d-glucuronic acid. The oligomeric structure of hUGDH is dynamic and can form two distinct hexameric complexes in solution. The active form of hUGDH consists of dimers that undergo a concentration-dependent association to form a hexamer with 32 symmetry. In the presence of the allosteric feedback inhibitor UDP-alpha-d-xylose (UDX), hUGDH changes shape to form an inactive, horseshoe-shaped complex. Previous studies have identified the UDX-induced allosteric mechanism that changes the hexameric structure to inhibit the enzyme. Here, we investigate the role of the 32 symmetry hexamer in the catalytic cycle. We engineered a stable hUGDH dimer by introducing a charge-switch substitution (K94E) in the hexamer-building interface (hUGDH(K94E)). The k(cat) of hUGDH(K94E) is approximately 160-fold lower than that of the wild-type enzyme, suggesting that the hexamer is the catalytically relevant state. We also show that cofactor binding triggers the formation of the 32 symmetry hexamer, but UDG is needed for the stability of the complex. The hUGDH(K94E) crystal structure at 2.08 A resolution identifies loop(88-110) as the cofactor-responsive allosteric switch that drives hexamer formation; loop(88-110) directly links cofactor binding to the stability of the hexamer-building interface. In the interface, loop(88-110) packs against the Thr131-loop/alpha6 helix, the allosteric switch that responds to the feedback inhibitor UDX. We also identify a structural element (the S-loop) that explains the indirect stabilization of the hexamer by substrate and supports a sequential, ordered binding of the substrate and cofactor. These observations support a model in which (i) UDG binds to the dimer and stabilizes the S-loop to promote cofactor binding and (ii) cofactor binding orders loop(88-110) to induce formation of the catalytically active hexamer.

-	~~==Function==~~	+	Cofactor Binding Triggers a Molecular Switch To Allosterically Activate Human UDP-alpha-d-glucose 6-Dehydrogenase.,Sennett NC, Kadirvelraj R, Wood ZA Biochemistry. 2012 Nov 20;51(46):9364-74. doi: 10.1021/bi301067w. Epub 2012 Nov, 8. PMID:23106432<ref>PMID:23106432</ref>
-	~~[[http~~:~~//www~~.~~uniprot~~.~~org~~/~~uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan~~, ~~chondroitin sulfate, and heparan sulfate~~.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4edf]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:023106432</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: UDP-glucose 6-dehydrogenase]]		[[Category: UDP-glucose 6-dehydrogenase]]
Line 21:		Line 31:
	[[Category: Oligomeric state]]		[[Category: Oligomeric state]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
-	[[Category: ~~Rossman~~ fold]]	+	[[Category: Rossmann fold]]

OCA at 08:51, 19 June 2013

OCA — Wed, 19 Jun 2013 08:51:45 GMT

←Older revision		Revision as of 08:51, 19 June 2013
Line 1:		Line 1:
-	[[Image:4edf.jpg\|left\|200px]]
-
	{{STRUCTURE_4edf\| PDB=4edf \| SCENE= }}		{{STRUCTURE_4edf\| PDB=4edf \| SCENE= }}
-
	===Dimeric hUGDH, K94E===		===Dimeric hUGDH, K94E===
-
	{{ABSTRACT_PUBMED_23106432}}		{{ABSTRACT_PUBMED_23106432}}
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.

	==About this Structure==		==About this Structure==
	[[4edf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA].		[[4edf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023106432</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: UDP-glucose 6-dehydrogenase]]		[[Category: UDP-glucose 6-dehydrogenase]]

OCA at 09:39, 21 November 2012

OCA — Wed, 21 Nov 2012 09:39:05 GMT

←Older revision		Revision as of 09:39, 21 November 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4edf.jpg\|left\|200px]]

-	~~The entry~~ 4edf ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4edf\| PDB=4edf \| SCENE= }}

-	~~Authors: Sennett~~, ~~N.C., Wood, Z.A.~~	+	===Dimeric hUGDH, K94E===

-	~~Description~~: ~~Dimeric hUGDH~~, ~~K94E~~	+	{{ABSTRACT_PUBMED_23106432}}
		+
		+	==About this Structure==
		+	[[4edf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDF OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: UDP-glucose 6-dehydrogenase]]
		+	[[Category: Sennett, N C.]]
		+	[[Category: Wood, Z A.]]
		+	[[Category: Glucuronidation]]
		+	[[Category: Mdr]]
		+	[[Category: Medium chain dehydrogenase]]
		+	[[Category: Molecular switch]]
		+	[[Category: Oligomeric state]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Rossman fold]]

OCA at 08:52, 25 April 2012

OCA — Wed, 25 Apr 2012 08:52:10 GMT

←Older revision		Revision as of 08:52, 25 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4edf is ON HOLD	+	The entry 4edf is ON HOLD until Paper Publication

	Authors: Sennett, N.C., Wood, Z.A.		Authors: Sennett, N.C., Wood, Z.A.

	Description: Dimeric hUGDH, K94E		Description: Dimeric hUGDH, K94E

OCA: Protected "4edf" [edit=sysop:move=sysop]

OCA — Wed, 04 Apr 2012 05:49:18 GMT

Protected "4edf" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:49, 4 April 2012