6svo - Revision history

OCA at 12:48, 24 January 2024

OCA — Wed, 24 Jan 2024 12:48:56 GMT

←Older revision		Revision as of 12:48, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6svo' size='340' side='right'caption='[[6svo]], [[Resolution\|resolution]] 2.33Å' scene=''>		<StructureSection load='6svo' size='340' side='right'caption='[[6svo]], [[Resolution\|resolution]] 2.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6svo]] 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=6SVO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6SVO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6svo]] 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=6SVO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SVO FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=AGP:2-DEOXY~~-2~~-AMINO+GLUCITOL-6-PHOSPHATE'>AGP</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</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]] 2.328Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~SEP~~:~~PHOSPHOSERINE~~'>~~SEP~~</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGP:2-DEOXY-2-AMINO+GLUCITOL-6-PHOSPHATE'>AGP</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">GFPT1~~, ~~GFAT, GFPT ([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=6svo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6svo OCA], [https://pdbe.org/6svo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6svo RCSB], [https://www.ebi.ac.uk/pdbsum/6svo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6svo 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/Glutamine--fructose-6-phosphate_transaminase_(isomerizing) Glutamine--fructose-6-phosphate transaminase (isomerizing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.16 2.6.1.16] </~~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=6svo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6svo OCA], [~~http~~://pdbe.org/6svo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6svo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6svo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6svo ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN]] Defects in GFPT1 are the cause of myasthenia, congenital, with tubular aggregates, type 1 (CMSTA1) [MIM:[~~http~~://omim.org/entry/610542 610542]]. A congenital myasthenic syndrome characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.<ref>PMID:21310273</ref>	+	[https://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN] Defects in GFPT1 are the cause of myasthenia, congenital, with tubular aggregates, type 1 (CMSTA1) [MIM:[https://omim.org/entry/610542 610542]. A congenital myasthenic syndrome characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.<ref>PMID:21310273</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN]] Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins.	+	[https://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN] Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6svo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6svo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aminotransferase 3D structures\|Aminotransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Allmeroth, K]]	+	[[Category: Allmeroth K]]
-	[[Category: Baumann, U]]	+	[[Category: Baumann U]]
-	[[Category: Denzel~~, M S~~]]	+	[[Category: Denzel MS]]
-	[[Category: Horn, M]]	+	[[Category: Horn M]]
-	[[Category: Pichlo, C]]	+	[[Category: Pichlo C]]
-	[[Category: Ruegenberg, S]]	+	[[Category: Ruegenberg S]]
-	~~[[Category: Gfat]]~~	+
-	~~[[Category: Glutamine fructose-6-phosphate aminotransferase]]~~	+
-	~~[[Category: Ntn hydrolase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:34, 19 February 2020

OCA — Wed, 19 Feb 2020 07:34:25 GMT

←Older revision		Revision as of 07:34, 19 February 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6svo is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of human GFAT-1 in complex with Glucosamine-6-Phosphate and L-Glu==
		+	<StructureSection load='6svo' size='340' side='right'caption='[[6svo]], [[Resolution\|resolution]] 2.33Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6svo]] 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=6SVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SVO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AGP:2-DEOXY-2-AMINO+GLUCITOL-6-PHOSPHATE'>AGP</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GFPT1, GFAT, GFPT ([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/Glutamine--fructose-6-phosphate_transaminase_(isomerizing) Glutamine--fructose-6-phosphate transaminase (isomerizing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.16 2.6.1.16] </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=6svo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6svo OCA], [http://pdbe.org/6svo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6svo RCSB], [http://www.ebi.ac.uk/pdbsum/6svo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6svo ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN]] Defects in GFPT1 are the cause of myasthenia, congenital, with tubular aggregates, type 1 (CMSTA1) [MIM:[http://omim.org/entry/610542 610542]]. A congenital myasthenic syndrome characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.<ref>PMID:21310273</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN]] Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Glutamine fructose-6-phosphate amidotransferase (GFAT) is the key enzyme in the hexosamine pathway (HP) that produces uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), linking energy metabolism with posttranslational protein glycosylation. In Caenorhabditis elegans, we previously identified gfat-1 gain-of-function mutations that elevate UDP-GlcNAc levels, improve protein homeostasis, and extend lifespan. GFAT is highly conserved, but the gain-of-function mechanism and its relevance in mammalian cells remained unclear. Here, we present the full-length crystal structure of human GFAT-1 in complex with various ligands and with important mutations. UDP-GlcNAc directly interacts with GFAT-1, inhibiting catalytic activity. The longevity-associated G451E variant shows drastically reduced sensitivity to UDP-GlcNAc inhibition in enzyme activity assays. Our structural and functional data point to a critical role of the interdomain linker in UDP-GlcNAc inhibition. In mammalian cells, the G451E variant potently activates the HP. Therefore, GFAT-1 gain-of-function through loss of feedback inhibition constitutes a potential target for the treatment of age-related proteinopathies.

-	~~Authors~~:	+	Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis.,Ruegenberg S, Horn M, Pichlo C, Allmeroth K, Baumann U, Denzel MS Nat Commun. 2020 Feb 4;11(1):687. doi: 10.1038/s41467-020-14524-5. PMID:32019926<ref>PMID:32019926</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6svo" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Allmeroth, K]]
		+	[[Category: Baumann, U]]
		+	[[Category: Denzel, M S]]
		+	[[Category: Horn, M]]
		+	[[Category: Pichlo, C]]
		+	[[Category: Ruegenberg, S]]
		+	[[Category: Gfat]]
		+	[[Category: Glutamine fructose-6-phosphate aminotransferase]]
		+	[[Category: Ntn hydrolase]]
		+	[[Category: Transferase]]

OCA: Protected "6svo" [edit=sysop:move=sysop]

OCA — Wed, 02 Oct 2019 07:53:27 GMT

Protected "6svo" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:53, 2 October 2019

OCA: New page: '''Unreleased structure''' The entry 6svo is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 02 Oct 2019 07:53:25 GMT

New page: '''Unreleased structure''' The entry 6svo is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6svo is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]