8d0i - Revision history

OCA at 10:05, 25 October 2023

OCA — Wed, 25 Oct 2023 10:05:07 GMT

←Older revision		Revision as of 10:05, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8d0i]] 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=8D0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D0I FirstGlance]. <br>		<table><tr><td colspan='2'>[[8d0i]] 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=8D0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D0I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PZ7:[[(2~{R},3~{S},4~{R},5~{R})-5-imidazo[2,1-f]purin-3-yl-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-5-[4-[(1~{S})-1-[methyl-[2,2,2-tris(fluoranyl)ethylcarbamoyl]amino]ethyl]pyridin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+hydrogen+phosphate'>PZ7</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]] 2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PZ7:[[(2~{R},3~{S},4~{R},5~{R})-5-imidazo[2,1-f]purin-3-yl-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-5-[4-[(1~{S})-1-[methyl-[2,2,2-tris(fluoranyl)ethylcarbamoyl]amino]ethyl]pyridin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+hydrogen+phosphate'>PZ7</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=8d0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d0i OCA], [https://pdbe.org/8d0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d0i RCSB], [https://www.ebi.ac.uk/pdbsum/8d0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d0i 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=8d0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d0i OCA], [https://pdbe.org/8d0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d0i RCSB], [https://www.ebi.ac.uk/pdbsum/8d0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d0i ProSAT]</span></td></tr>
	</table>		</table>

OCA at 11:07, 30 November 2022

OCA — Wed, 30 Nov 2022 11:07:08 GMT

←Older revision		Revision as of 11:07, 30 November 2022
Line 8:		Line 8:
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/SARM1_HUMAN SARM1_HUMAN]] Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.<ref>PMID:15123841</ref> <ref>PMID:16964262</ref> <ref>PMID:16985498</ref> <ref>PMID:20306472</ref>	+	[https://www.uniprot.org/uniprot/SARM1_HUMAN SARM1_HUMAN] Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.<ref>PMID:15123841</ref> <ref>PMID:16964262</ref> <ref>PMID:16985498</ref> <ref>PMID:20306472</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:47, 21 September 2022

OCA — Wed, 21 Sep 2022 07:47:08 GMT

←Older revision		Revision as of 07:47, 21 September 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 8d0i is ~~ON HOLD until Paper~~ Publication	+	==Human SARM1 bound to an NB-3 eADPR adduct==
		+	<StructureSection load='8d0i' size='340' side='right'caption='[[8d0i]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8d0i]] 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=8D0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D0I FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PZ7:[[(2~{R},3~{S},4~{R},5~{R})-5-imidazo[2,1-f]purin-3-yl-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-5-[4-[(1~{S})-1-[methyl-[2,2,2-tris(fluoranyl)ethylcarbamoyl]amino]ethyl]pyridin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+hydrogen+phosphate'>PZ7</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=8d0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d0i OCA], [https://pdbe.org/8d0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d0i RCSB], [https://www.ebi.ac.uk/pdbsum/8d0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d0i ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/SARM1_HUMAN SARM1_HUMAN]] Negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway which plays a pivotal role in activating axonal degeneration following injury. Promotes Wallerian degeneration an injury-induced axonal death pathway which involves degeneration of an axon distal to the injury site. Can activate neuronal death in response to stress. Regulates dendritic arborization through the MAPK4-JNK pathway. Involved in innate immune response. Inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38.<ref>PMID:15123841</ref> <ref>PMID:16964262</ref> <ref>PMID:16985498</ref> <ref>PMID:20306472</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Axon degeneration is an early pathological event in many neurological diseases. The identification of the nicotinamide adenine dinucleotide (NAD) hydrolase SARM1 as a central metabolic sensor and axon executioner presents an exciting opportunity to develop novel neuroprotective therapies that can prevent or halt the degenerative process, yet limited progress has been made on advancing efficacious inhibitors. We describe a class of NAD-dependent active-site SARM1 inhibitors that function by intercepting NAD hydrolysis and undergoing covalent conjugation with the reaction product adenosine diphosphate ribose (ADPR). The resulting small-molecule ADPR adducts are highly potent and confer compelling neuroprotection in preclinical models of neurological injury and disease, validating this mode of inhibition as a viable therapeutic strategy. Additionally, we show that the most potent inhibitor of CD38, a related NAD hydrolase, also functions by the same mechanism, further underscoring the broader applicability of this mechanism in developing therapies against this class of enzymes.

-	~~Authors~~:	+	Uncompetitive, adduct-forming SARM1 inhibitors are neuroprotective in preclinical models of nerve injury and disease.,Bratkowski M, Burdett TC, Danao J, Wang X, Mathur P, Gu W, Beckstead JA, Talreja S, Yang YS, Danko G, Park JH, Walton M, Brown SP, Tegley CM, Joseph PRB, Reynolds CH, Sambashivan S Neuron. 2022 Sep 7. pii: S0896-6273(22)00749-8. doi:, 10.1016/j.neuron.2022.08.017. PMID:36087583<ref>PMID:36087583</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8d0i" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Bratkowski MA]]
		+	[[Category: Mathur P]]

OCA at 04:12, 13 July 2022

OCA — Wed, 13 Jul 2022 04:12:15 GMT

←Older revision		Revision as of 04:12, 13 July 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8d0i is ON HOLD	+	The entry 8d0i is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8d0i" [edit=sysop:move=sysop]

OCA — Wed, 08 Jun 2022 04:30:55 GMT

Protected "8d0i" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:30, 8 June 2022

OCA: New page: '''Unreleased structure''' The entry 8d0i is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 08 Jun 2022 04:30:54 GMT

New page: '''Unreleased structure''' The entry 8d0i is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8d0i is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]