6fwz - Revision history

OCA at 17:24, 20 November 2019

OCA — Wed, 20 Nov 2019 17:24:10 GMT

←Older revision		Revision as of 17:24, 20 November 2019
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	==Crystal structure of human UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) (V264G mutant) in complex with UDP-GlcNAc==		==Crystal structure of human UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) (V264G mutant) in complex with UDP-GlcNAc==
-	<StructureSection load='6fwz' size='340' side='right' caption='[[6fwz]], [[Resolution\|resolution]] 3.10Å' scene=''>	+	<StructureSection load='6fwz' size='340' side='right'caption='[[6fwz]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6fwz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FWZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6fwz]] is a 1 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=6FWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FWZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=P6L:(2S)-3-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-2-[(6E)-HEXADEC-6-ENOYLOXY]PROPYL+(8E)-OCTADEC-8-ENOATE'>P6L</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=P6L:(2S)-3-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-2-[(6E)-HEXADEC-6-ENOYLOXY]PROPYL+(8E)-OCTADEC-8-ENOATE'>P6L</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DPAGT1, DPAGT2 ([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-N-acetylglucosamine--dolichyl-phosphate_N-acetylglucosaminephosphotransferase UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.8.15 2.7.8.15] </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-N-acetylglucosamine--dolichyl-phosphate_N-acetylglucosaminephosphotransferase UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.8.15 2.7.8.15] </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=6fwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fwz OCA], [http://pdbe.org/6fwz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fwz RCSB], [http://www.ebi.ac.uk/pdbsum/6fwz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fwz 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=6fwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fwz OCA], [http://pdbe.org/6fwz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fwz RCSB], [http://www.ebi.ac.uk/pdbsum/6fwz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fwz ProSAT]</span></td></tr>
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN]] Catalyzes the initial step in the synthesis of dolichol-P-P-oligosaccharides.		[[http://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN]] Catalyzes the initial step in the synthesis of dolichol-P-P-oligosaccharides.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic "lipid-altered" tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.
		+
		+	Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.,Dong YY, Wang H, Pike ACW, Cochrane SA, Hamedzadeh S, Wyszynski FJ, Bushell SR, Royer SF, Widdick DA, Sajid A, Boshoff HI, Park Y, Lucas R, Liu WM, Lee SS, Machida T, Minall L, Mehmood S, Belaya K, Liu WW, Chu A, Shrestha L, Mukhopadhyay SMM, Strain-Damerell C, Chalk R, Burgess-Brown NA, Bibb MJ, Barry Iii CE, Robinson CV, Beeson D, Davis BG, Carpenter EP Cell. 2018 Nov 1;175(4):1045-1058.e16. doi: 10.1016/j.cell.2018.10.037. PMID:30388443<ref>PMID:30388443</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6fwz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase]]		[[Category: UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]

OCA at 07:23, 25 July 2018

OCA — Wed, 25 Jul 2018 07:23:02 GMT

←Older revision		Revision as of 07:23, 25 July 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6fwz is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Crystal structure of human UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) (V264G mutant) in complex with UDP-GlcNAc==
-		+	<StructureSection load='6fwz' size='340' side='right' caption='[[6fwz]], [[Resolution\|resolution]] 3.10Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6fwz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FWZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FWZ FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=P6L:(2S)-3-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-2-[(6E)-HEXADEC-6-ENOYLOXY]PROPYL+(8E)-OCTADEC-8-ENOATE'>P6L</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-N-acetylglucosamine--dolichyl-phosphate_N-acetylglucosaminephosphotransferase UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.8.15 2.7.8.15] </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=6fwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fwz OCA], [http://pdbe.org/6fwz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fwz RCSB], [http://www.ebi.ac.uk/pdbsum/6fwz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fwz ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN]] DPAGT1-CDG;Congenital myasthenic syndromes with glycosylation defect. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN]] Catalyzes the initial step in the synthesis of dolichol-P-P-oligosaccharides.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase]]
		+	[[Category: Arrowsmith, C H]]
		+	[[Category: Beeson, D]]
		+	[[Category: Belaya, K]]
		+	[[Category: Berridge, G]]
		+	[[Category: Bountra, C]]
		+	[[Category: Burgess-Brown, N]]
		+	[[Category: Carpenter, E P]]
		+	[[Category: Chalk, R]]
		+	[[Category: Chu, A]]
		+	[[Category: Dong, L]]
		+	[[Category: Dong, Y Y]]
		+	[[Category: Edwards, A M]]
		+	[[Category: Goubin, S]]
		+	[[Category: Kupinska, K]]
		+	[[Category: Mahajan, P]]
		+	[[Category: Mukhopadhyay, S]]
		+	[[Category: Pike, A C.W]]
		+	[[Category: Structural genomic]]
		+	[[Category: Tessitore, A]]
		+	[[Category: Wang, D]]
		+	[[Category: Antibiotic]]
		+	[[Category: Congenital myasthenic syndrome]]
		+	[[Category: Integral membrane protein]]
		+	[[Category: Pnpt]]
		+	[[Category: Protein glycosylation]]
		+	[[Category: Sgc]]
		+	[[Category: Transferase]]

OCA at 05:25, 28 March 2018

OCA — Wed, 28 Mar 2018 05:25:11 GMT

←Older revision		Revision as of 05:25, 28 March 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6fwz is ON HOLD	+	The entry 6fwz is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 06:18, 21 March 2018

OCA — Wed, 21 Mar 2018 06:18:27 GMT

←Older revision		Revision as of 06:18, 21 March 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6fwz is ON HOLD ~~until sometime in the future~~	+	The entry 6fwz is ON HOLD

	Authors:		Authors:

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

OCA — Wed, 14 Mar 2018 05:19:00 GMT

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

←Older revision

Revision as of 05:19, 14 March 2018

OCA: New page: '''Unreleased structure''' The entry 6fwz is ON HOLD until sometime in the future Authors: Description: Category: Unreleased Structures

OCA — Wed, 14 Mar 2018 05:18:58 GMT

New page: '''Unreleased structure''' The entry 6fwz is ON HOLD until sometime in the future Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6fwz is ON HOLD until sometime in the future

Authors:

Description:
[[Category: Unreleased Structures]]