OCA at 14:04, 29 November 2023

OCA — Wed, 29 Nov 2023 14:04:00 GMT

←Older revision		Revision as of 14:04, 29 November 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8p0l is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of human O-GlcNAcase in complex with an S-linked CKII peptide==
		+	<StructureSection load='8p0l' size='340' side='right'caption='[[8p0l]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8p0l]] 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=8P0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8P0L 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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SER:SERINE'>SER</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=8p0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8p0l OCA], [https://pdbe.org/8p0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8p0l RCSB], [https://www.ebi.ac.uk/pdbsum/8p0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8p0l ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/OGA_HUMAN OGA_HUMAN] Isoform 1: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) (PubMed:11148210). Does not bind acetyl-CoA and does not have histone acetyltransferase activity (PubMed:24088714).<ref>PMID:11148210</ref> <ref>PMID:11788610</ref> <ref>PMID:20673219</ref> <ref>PMID:22365600</ref> <ref>PMID:24088714</ref> Isoform 3: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro), but has about six times lower specific activity than isoform 1.<ref>PMID:20673219</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human O-linked beta-N-acetylglucosaminidase (hOGA) is one of the two enzymes involved in nuclear and cytoplasmic protein O-GlcNAcylation, an essential post-translational modification. The enzyme catalyzes the hydrolysis of the GlcNAc-O-(Ser/Thr) glycosidic bonds via anchimeric assistance through the 2-acetamido group of the GlcNAc sugar. However, the conformational itinerary of the GlcNAc ring during catalysis remains unclear. Here we report the crystal structure of wild type hOGA in complex with a nonhydrolyzable glycopeptide substrate and elucidate the full enzyme catalytic mechanism using QM/MM metadynamics. We show that the enzyme can bind the substrate in either a chair- or a boat-like conformation, but only the latter is catalytically competent, leading to the reaction products via (1,4)B/(1)S(3) --> [(4)E](double dagger) --> (4)C(1) and (4)C(1) --> [(4)E](double dagger) --> (1,4)B/(1)S(3) conformational itineraries for the first and second catalytic reaction steps, respectively. Our results reconcile previous experimental observations for human and bacterial OGA and will aid the development of more effective OGA inhibitors for diseases associated with impaired O-GlcNAcylation.

-	~~Authors: Males, A., Davies, G~~.J., Calvelo, M., Alteen, ~~M.G.~~, Vocadlo, ~~D.J.~~, Rovira, C.	+	Human O-GlcNAcase Uses a Preactivated Boat-skew Substrate Conformation for Catalysis. Evidence from X-ray Crystallography and QM/MM Metadynamics.,Calvelo M, Males A, Alteen MG, Willems LI, Vocadlo DJ, Davies GJ, Rovira C ACS Catal. 2023 Oct 10;13(20):13672-13678. doi: 10.1021/acscatal.3c02378. , eCollection 2023 Oct 20. PMID:37969138<ref>PMID:37969138</ref>

-	~~Description: Crystal structure~~ of ~~human O-GlcNAcase in complex with an~~ S-~~linked CKII peptide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Davies, G.J~~]]	+	<div class="pdbe-citations 8p0l" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Rovira, C~~]]	+	== References ==
-	[[Category: ~~Alteen,~~ M.G]]	+	<references/>
-	[[Category: Males, A]]	+	__TOC__
-	[[Category: ~~Vocadlo, D.J~~]]	+	</StructureSection>
-	[[Category: ~~Calvelo, M~~]]	+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Alteen MG]]
		+	[[Category: Calvelo M]]
		+	[[Category: Davies GJ]]
		+	[[Category: Males A]]
		+	[[Category: Rovira C]]
		+	[[Category: Vocadlo DJ]]

OCA at 08:15, 21 June 2023

OCA — Wed, 21 Jun 2023 08:15:53 GMT

←Older revision		Revision as of 08:15, 21 June 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8p0l is ON HOLD	+	The entry 8p0l is ON HOLD until Paper Publication

	Authors: Males, A., Davies, G.J., Calvelo, M., Alteen, M.G., Vocadlo, D.J., Rovira, C.		Authors: Males, A., Davies, G.J., Calvelo, M., Alteen, M.G., Vocadlo, D.J., Rovira, C.
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	Description: Crystal structure of human O-GlcNAcase in complex with an S-linked CKII peptide		Description: Crystal structure of human O-GlcNAcase in complex with an S-linked CKII peptide
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Males, A]]
-	[[Category: Vocadlo, D.J]]
-	[[Category: Calvelo, M]]
	[[Category: Davies, G.J]]		[[Category: Davies, G.J]]
	[[Category: Rovira, C]]		[[Category: Rovira, C]]
	[[Category: Alteen, M.G]]		[[Category: Alteen, M.G]]
		+	[[Category: Males, A]]
		+	[[Category: Vocadlo, D.J]]
		+	[[Category: Calvelo, M]]

OCA: Protected "8p0l" [edit=sysop:move=sysop]

OCA — Thu, 18 May 2023 05:44:40 GMT

Protected "8p0l" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:44, 18 May 2023

OCA: New page: '''Unreleased structure''' The entry 8p0l is ON HOLD Authors: Males, A., Davies, G.J., Calvelo, M., Alteen, M.G., Vocadlo, D.J., Rovira, C. Description: Crystal structure of human O-Gl...

OCA — Thu, 18 May 2023 05:44:38 GMT

New page: '''Unreleased structure''' The entry 8p0l is ON HOLD Authors: Males, A., Davies, G.J., Calvelo, M., Alteen, M.G., Vocadlo, D.J., Rovira, C. Description: Crystal structure of human O-Gl...

New page

'''Unreleased structure'''

The entry 8p0l is ON HOLD

Authors: Males, A., Davies, G.J., Calvelo, M., Alteen, M.G., Vocadlo, D.J., Rovira, C.

Description: Crystal structure of human O-GlcNAcase in complex with an S-linked CKII peptide
[[Category: Unreleased Structures]]
[[Category: Males, A]]
[[Category: Vocadlo, D.J]]
[[Category: Calvelo, M]]
[[Category: Davies, G.J]]
[[Category: Rovira, C]]
[[Category: Alteen, M.G]]

8p0l - Revision history

OCA at 14:04, 29 November 2023

OCA at 08:15, 21 June 2023

OCA: Protected "8p0l" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8p0l is ON HOLD Authors: Males, A., Davies, G.J., Calvelo, M., Alteen, M.G., Vocadlo, D.J., Rovira, C. Description: Crystal structure of human O-Gl...