7nah - Revision history

OCA at 16:26, 18 October 2023

2023-10-18T16:26:20Z

←Older revision		Revision as of 16:26, 18 October 2023
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	<StructureSection load='7nah' size='340' side='right'caption='[[7nah]], [[Resolution\|resolution]] 1.79Å' scene=''>		<StructureSection load='7nah' size='340' side='right'caption='[[7nah]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7nah]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NAH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7nah]] 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=7NAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NAH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1OF:[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-(8-oxidanylidene-7~{H}-2,7-naphthyridin-2-yl)oxolan-2-yl]methyl+hydrogen+phosphate'>1OF</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]] 1.79Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1OF:[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-(8-oxidanylidene-7~{H}-2,7-naphthyridin-2-yl)oxolan-2-yl]methyl+hydrogen+phosphate'>1OF</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=7nah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nah OCA], [https://pdbe.org/7nah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nah RCSB], [https://www.ebi.ac.uk/pdbsum/7nah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nah 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=7nah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nah OCA], [https://pdbe.org/7nah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nah RCSB], [https://www.ebi.ac.uk/pdbsum/7nah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nah ProSAT]</span></td></tr>
	</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 ==
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	</div>		</div>
	<div class="pdbe-citations 7nah" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7nah" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[SARM1 3D structures\|SARM1 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Shi, Y]]	+	[[Category: Shi Y]]
-	[[Category: Ve, T]]	+	[[Category: Ve T]]
-	~~[[Category: Axon degeneration]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Nadase~~]]	+

OCA at 10:34, 6 April 2022

2022-04-06T10:34:35Z

←Older revision		Revision as of 10:34, 6 April 2022
Line 1:		Line 1:

	==Crystal structure of the TIR domain from human SARM1 in complex with 2AD==		==Crystal structure of the TIR domain from human SARM1 in complex with 2AD==
-	<StructureSection load='7nah' size='340' side='right'caption='[[7nah]]' scene=''>	+	<StructureSection load='7nah' size='340' side='right'caption='[[7nah]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NAH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7nah]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NAH FirstGlance]. <br>
-	</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=7nah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nah OCA], [https://pdbe.org/7nah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nah RCSB], [https://www.ebi.ac.uk/pdbsum/7nah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nah ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1OF:[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-(8-oxidanylidene-7~{H}-2,7-naphthyridin-2-yl)oxolan-2-yl]methyl+hydrogen+phosphate'>1OF</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=7nah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nah OCA], [https://pdbe.org/7nah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nah RCSB], [https://www.ebi.ac.uk/pdbsum/7nah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nah ProSAT]</span></td></tr>
	</table>		</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 ==
		+	The NADase SARM1 (sterile alpha and TIR motif containing 1) is a key executioner of axon degeneration and a therapeutic target for several neurodegenerative conditions. We show that a potent SARM1 inhibitor undergoes base exchange with the nicotinamide moiety of nicotinamide adenine dinucleotide (NAD(+)) to produce the bona fide inhibitor 1AD. We report structures of SARM1 in complex with 1AD, NAD(+) mimetics and the allosteric activator nicotinamide mononucleotide (NMN). NMN binding triggers reorientation of the armadillo repeat (ARM) domains, which disrupts ARM:TIR interactions and leads to formation of a two-stranded TIR domain assembly. The active site spans two molecules in these assemblies, explaining the requirement of TIR domain self-association for NADase activity and axon degeneration. Our results reveal the mechanisms of SARM1 activation and substrate binding, providing rational avenues for the design of new therapeutics targeting SARM1.
		+
		+	Structural basis of SARM1 activation, substrate recognition, and inhibition by small molecules.,Shi Y, Kerry PS, Nanson JD, Bosanac T, Sasaki Y, Krauss R, Saikot FK, Adams SE, Mosaiab T, Masic V, Mao X, Rose F, Vasquez E, Furrer M, Cunnea K, Brearley A, Gu W, Luo Z, Brillault L, Landsberg MJ, Di Antonio A, Kobe B, Milbrandt J, Hughes RO, Ve T Mol Cell. 2022 Mar 18. pii: S1097-2765(22)00216-7. doi:, 10.1016/j.molcel.2022.03.007. PMID:35334231<ref>PMID:35334231</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7nah" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Shi Y]]	+	[[Category: Shi, Y]]
-	[[Category: Ve T]]	+	[[Category: Ve, T]]
		+	[[Category: Axon degeneration]]
		+	[[Category: Hydrolase]]
		+	[[Category: Nadase]]

OCA at 11:17, 23 March 2022

2022-03-23T11:17:24Z

←Older revision		Revision as of 11:17, 23 March 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7nah ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of the TIR domain from human SARM1 in complex with 2AD==
-		+	<StructureSection load='7nah' size='340' side='right'caption='[[7nah]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NAH FirstGlance]. <br>
-	~~Description~~:	+	</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=7nah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nah OCA], [https://pdbe.org/7nah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nah RCSB], [https://www.ebi.ac.uk/pdbsum/7nah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nah ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Shi Y]]
		+	[[Category: Ve T]]

OCA at 09:25, 28 July 2021

2021-07-28T09:25:59Z

←Older revision		Revision as of 09:25, 28 July 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7nah is ON HOLD	+	The entry 7nah is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7nah" [edit=sysop:move=sysop]

2021-07-02T02:31:13Z

Protected "7nah" [edit=sysop:move=sysop]

←Older revision

Revision as of 02:31, 2 July 2021

OCA: New page: '''Unreleased structure''' The entry 7nah is ON HOLD Authors: Description: Category: Unreleased Structures

2021-07-02T02:31:12Z

New page: '''Unreleased structure''' The entry 7nah is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7nah is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]