5uxh - Revision history

OCA at 13:36, 4 October 2023

OCA — Wed, 04 Oct 2023 13:36:54 GMT

←Older revision		Revision as of 13:36, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5uxh' size='340' side='right'caption='[[5uxh]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='5uxh' size='340' side='right'caption='[[5uxh]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5uxh]] is a 2 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=5UXH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5UXH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5uxh]] is a 2 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=5UXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UXH FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=GFB:GUANOSINE-5-DIPHOSPHATE-BETA-L-FUCOPYRANOSE'>GFB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.41Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[5ux6\|5ux6~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GFB:GUANOSINE-5-DIPHOSPHATE-BETA-L-FUCOPYRANOSE'>GFB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>POFUT1, FUT12, KIAA0180 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</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=5uxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxh OCA], [https://pdbe.org/5uxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uxh RCSB], [https://www.ebi.ac.uk/pdbsum/5uxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxh ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Peptide~~-O-~~fucosyltransferase Peptide~~-~~O-fucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.221 2.4.1.221]~~ </~~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=5uxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxh OCA], [~~http~~://pdbe.org/5uxh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5uxh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5uxh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxh ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/OFUT1_HUMAN OFUT1_HUMAN]] Dowling-Degos disease. The disease is caused by mutations affecting the gene represented in this entry.	+	[https://www.uniprot.org/uniprot/OFUT1_HUMAN OFUT1_HUMAN] Dowling-Degos disease. The disease is caused by mutations affecting the gene represented in this entry.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/OFUT1_HUMAN OFUT1_HUMAN]] Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).<ref>PMID:11524432</ref> <ref>PMID:8358148</ref>	+	[https://www.uniprot.org/uniprot/OFUT1_HUMAN OFUT1_HUMAN] Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).<ref>PMID:11524432</ref> <ref>PMID:8358148</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Peptide-O-fucosyltransferase]]~~	+	[[Category: Blacklow SC]]
-	[[Category: Blacklow~~, S C~~]]	+	[[Category: McMillan B]]
-	[[Category: McMillan, B]]	+	[[Category: Xu X]]
-	[[Category: Xu, X]]	+
-	~~[[Category: Gdp-fucose]]~~	+
-	~~[[Category: Notch signaling]]~~	+
-	~~[[Category: Pofut1]]~~	+
-	~~[[Category: T-all]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:32, 4 December 2019

OCA — Wed, 04 Dec 2019 09:32:39 GMT

←Older revision		Revision as of 09:32, 4 December 2019
Line 1:		Line 1:

	==Structure of Human POFUT1 in complex with GDP-fucose==		==Structure of Human POFUT1 in complex with GDP-fucose==
-	<StructureSection load='5uxh' size='340' side='right' caption='[[5uxh]], [[Resolution\|resolution]] 2.41Å' scene=''>	+	<StructureSection load='5uxh' size='340' side='right'caption='[[5uxh]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5uxh]] is a 2 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=5UXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UXH FirstGlance]. <br>		<table><tr><td colspan='2'>[[5uxh]] is a 2 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=5UXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UXH FirstGlance]. <br>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Peptide-O-fucosyltransferase]]		[[Category: Peptide-O-fucosyltransferase]]
	[[Category: Blacklow, S C]]		[[Category: Blacklow, S C]]

OCA at 14:37, 6 November 2017

OCA — Mon, 06 Nov 2017 14:37:49 GMT

←Older revision		Revision as of 14:37, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='5uxh' size='340' side='right' caption='[[5uxh]], [[Resolution\|resolution]] 2.41Å' scene=''>		<StructureSection load='5uxh' size='340' side='right' caption='[[5uxh]], [[Resolution\|resolution]] 2.41Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5uxh]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UXH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5uxh]] is a 2 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=5UXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UXH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GFB:GUANOSINE-5-DIPHOSPHATE-BETA-L-FUCOPYRANOSE'>GFB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GFB:GUANOSINE-5-DIPHOSPHATE-BETA-L-FUCOPYRANOSE'>GFB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ux6\|5ux6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ux6\|5ux6]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POFUT1, FUT12, KIAA0180 ([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/Peptide-O-fucosyltransferase Peptide-O-fucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.221 2.4.1.221] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptide-O-fucosyltransferase Peptide-O-fucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.221 2.4.1.221] </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=5uxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxh OCA], [http://pdbe.org/5uxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uxh RCSB], [http://www.ebi.ac.uk/pdbsum/5uxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxh 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=5uxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxh OCA], [http://pdbe.org/5uxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uxh RCSB], [http://www.ebi.ac.uk/pdbsum/5uxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxh ProSAT]</span></td></tr>
Line 26:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Peptide-O-fucosyltransferase]]		[[Category: Peptide-O-fucosyltransferase]]
	[[Category: Blacklow, S C]]		[[Category: Blacklow, S C]]

OCA at 13:17, 5 April 2017

OCA — Wed, 05 Apr 2017 13:17:45 GMT

←Older revision		Revision as of 13:17, 5 April 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5uxh~~ is ~~ON HOLD~~	+	==Structure of Human POFUT1 in complex with GDP-fucose==
		+	<StructureSection load='5uxh' size='340' side='right' caption='[[5uxh]], [[Resolution\|resolution]] 2.41Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5uxh]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UXH FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GFB:GUANOSINE-5-DIPHOSPHATE-BETA-L-FUCOPYRANOSE'>GFB</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ux6\|5ux6]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptide-O-fucosyltransferase Peptide-O-fucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.221 2.4.1.221] </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=5uxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxh OCA], [http://pdbe.org/5uxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uxh RCSB], [http://www.ebi.ac.uk/pdbsum/5uxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxh ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/OFUT1_HUMAN OFUT1_HUMAN]] Dowling-Degos disease. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/OFUT1_HUMAN OFUT1_HUMAN]] Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).<ref>PMID:11524432</ref> <ref>PMID:8358148</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein O-fucosyltransferase-1 (POFUT1), which transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins, is essential for Notch signal transduction in mammals. Here, we examine the consequences of POFUT1 loss on the oncogenic signaling associated with certain leukemia-associated mutations of human Notch1, report the structures of human POFUT1 in free and GDP-fucose bound states, and assess the effects of Dowling-Degos mutations on human POFUT1 function. CRISPR-mediated knockout of POFUT1 in U2OS cells suppresses both normal Notch1 signaling, and the ligand-independent signaling associated with leukemogenic mutations of Notch1. Normal and oncogenic signaling are rescued by wild-type POFUT1 but rescue is impaired by an active-site R240A mutation. The overall structure of the human enzyme closely resembles that of the Caenorhabditis elegans protein, with an overall backbone RMSD of 0.93 A, despite primary sequence identity of only 39% in the mature protein. GDP-fucose binding to the human enzyme induces limited backbone conformational movement, though the side chains of R43 and D244 reorient to make direct contact with the fucose moiety in the complex. The reported Dowling-Degos mutations of POFUT1, except for M262T, fail to rescue Notch1 signaling efficiently in the CRISPR-engineered POFUT1-/- background. Together, these studies identify POFUT1 as a potential target for cancers driven by Notch1 mutations and provide a structural roadmap for its inhibition.

-	~~Authors: Xu~~, X., ~~Blacklow~~, S.C.	+	Structure of human POFUT1, its requirement in ligand-independent oncogenic Notch signaling, and functional effects of Dowling-Degos mutations.,McMillan BJ, Zimmerman B, Egan ED, Lofgren M, Xu X, Hesser A, Blacklow SC Glycobiology. 2017 Mar 17:1-10. doi: 10.1093/glycob/cwx020. PMID:28334865<ref>PMID:28334865</ref>

-	~~Description: Structure~~ of ~~Human POFUT1 in its apo form~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5uxh" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Peptide-O-fucosyltransferase]]
		+	[[Category: Blacklow, S C]]
		+	[[Category: McMillan, B]]
	[[Category: Xu, X]]		[[Category: Xu, X]]
-	[[Category: ~~Blacklow, S.C~~]]	+	[[Category: Gdp-fucose]]
		+	[[Category: Notch signaling]]
		+	[[Category: Pofut1]]
		+	[[Category: T-all]]
		+	[[Category: Transferase]]

OCA at 19:29, 15 March 2017

OCA — Wed, 15 Mar 2017 19:29:00 GMT

←Older revision		Revision as of 19:29, 15 March 2017
Line 3:		Line 3:
	The entry 5uxh is ON HOLD		The entry 5uxh is ON HOLD

-	Authors: ~~Xiang~~ Xu, ~~Stephen~~ Blacklow	+	Authors: Xu, X., Blacklow, S.C.

-	Description: Structure of Human POFUT1 in its apo form.	+	Description: Structure of Human POFUT1 in its apo form
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~Xiang~~ Xu, ~~Stephen~~ Blacklow]]	+	[[Category: Xu, X]]
		+	[[Category: Blacklow, S.C]]

OCA: Protected "5uxh" [edit=sysop:move=sysop]

OCA — Thu, 09 Mar 2017 15:03:46 GMT

Protected "5uxh" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:03, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5uxh is ON HOLD Authors: Xiang Xu, Stephen Blacklow Description: Structure of Human POFUT1 in its apo form. Category: Unreleased Structures [[C...

OCA — Thu, 09 Mar 2017 15:03:44 GMT

New page: '''Unreleased structure''' The entry 5uxh is ON HOLD Authors: Xiang Xu, Stephen Blacklow Description: Structure of Human POFUT1 in its apo form. Category: Unreleased Structures [[C...

New page

'''Unreleased structure'''

The entry 5uxh is ON HOLD

Authors: Xiang Xu, Stephen Blacklow

Description: Structure of Human POFUT1 in its apo form.
[[Category: Unreleased Structures]]
[[Category: Xiang Xu, Stephen Blacklow]]