6jx6 - Revision history

OCA at 10:21, 22 November 2023

2023-11-22T10:21:18Z

←Older revision		Revision as of 10:21, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='6jx6' size='340' side='right'caption='[[6jx6]], [[Resolution\|resolution]] 2.81Å' scene=''>		<StructureSection load='6jx6' size='340' side='right'caption='[[6jx6]], [[Resolution\|resolution]] 2.81Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6jx6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JX6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6JX6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6jx6]] is a 4 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=6JX6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JX6 FirstGlance]. <br>
-	</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=6jx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jx6 OCA], [~~http~~://pdbe.org/6jx6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6jx6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6jx6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6jx6 ProSAT]</span></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]] 2.805Å</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=6jx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jx6 OCA], [https://pdbe.org/6jx6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jx6 RCSB], [https://www.ebi.ac.uk/pdbsum/6jx6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jx6 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:[~~http~~://omim.org/entry/614152 614152]]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:21722859</ref>	+	[https://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN] Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:[https://omim.org/entry/614152 614152]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:21722859</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.<ref>PMID:10929711</ref> <ref>PMID:14523016</ref> <ref>PMID:15200957</ref>	+	[https://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN] Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.<ref>PMID:10929711</ref> <ref>PMID:14523016</ref> <ref>PMID:15200957</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Nayak, D]]	+	[[Category: Nayak D]]
-	[[Category: Ng, J]]	+	[[Category: Ng J]]
-	[[Category: Singh, S]]	+	[[Category: Singh S]]
-	[[Category: Sivaraman, J]]	+	[[Category: Sivaraman J]]
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Smac~~]]	+

OCA at 08:04, 4 December 2019

2019-12-04T08:04:28Z

←Older revision		Revision as of 08:04, 4 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6jx6 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Tetrameric form of Smac==
		+	<StructureSection load='6jx6' size='340' side='right'caption='[[6jx6]], [[Resolution\|resolution]] 2.81Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6jx6]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JX6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JX6 FirstGlance]. <br>
		+	</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=6jx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jx6 OCA], [http://pdbe.org/6jx6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jx6 RCSB], [http://www.ebi.ac.uk/pdbsum/6jx6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jx6 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:[http://omim.org/entry/614152 614152]]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:21722859</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.<ref>PMID:10929711</ref> <ref>PMID:14523016</ref> <ref>PMID:15200957</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The HECT E3 ligase family comprises three subfamilies: NEDD4 E3 ubiquitin protein ligase (NEDD4), HECT and RLD domain-containing E3 ubiquitin protein ligase (HERC), and "other." Most previous studies have focused on the NEDD4 subfamily. Apoptosis-resistant E3 ligase 1 (AREL1) belongs to "other" subfamily HECT that inhibits apoptosis by ubiquitinating and degrading proapoptotic proteins. Here, we report the crystal structure of the extended HECT domain of AREL1 (436-823 aa) at 2.4 A resolution and its ubiquitination of the proapoptotic protein second mitochondria-derived activator of caspase (SMAC). We found that the extended HECT domain adopts an inverted, T-shaped, bilobed conformation and harbors an additional loop (567-573 aa) absent in all other HECT members. We also show that the N-terminal extended region (436-482 aa) preceding the HECT domain is indispensable for its stability and activity and that without this region, the HECT domain becomes inactive. AREL1 ubiquitinated SMAC, primarily on Lys-62 and Lys-191. We solved the crystal structure of tetrameric form of SMAC to 2.8 A resolution, revealing the Lys-62 and Lys-191 locations. The AREL1 HECT domain assembled Lys-33-, Lys-48- and Lys-63-linked polyubiquitin chains. Moreover, E701A substitution in the AREL1 HECT domain substantially increased its autopolyubiquitination and SMAC ubiquitination activity, whereas deletion of the last three amino acids at the C terminus completely abrogated AREL1 autoubiquitination and reduced SMAC ubiquitination. Finally, an AREL1-specific ubiquitin variant inhibited SMAC ubiquitination in vitro. Our findings may assist in the development of AREL1 inhibitors that block its anti-apoptotic activity in cancer.

-	~~Authors~~:	+	Structural insights into a HECT-type E3 ligase AREL1 and its ubiquitination activities in vitro.,Singh S, Ng J, Nayak D, Sivaraman J J Biol Chem. 2019 Nov 15. pii: RA119.010327. doi: 10.1074/jbc.RA119.010327. PMID:31732561<ref>PMID:31732561</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6jx6" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Nayak, D]]
		+	[[Category: Ng, J]]
		+	[[Category: Singh, S]]
		+	[[Category: Sivaraman, J]]
		+	[[Category: Apoptosis]]
		+	[[Category: Smac]]

OCA at 20:56, 5 June 2019

2019-06-05T20:56:16Z

←Older revision		Revision as of 20:56, 5 June 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6jx6 is ON HOLD	+	The entry 6jx6 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6jx6" [edit=sysop:move=sysop]

2019-05-01T06:58:43Z

Protected "6jx6" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:58, 1 May 2019

OCA: New page: '''Unreleased structure''' The entry 6jx6 is ON HOLD Authors: Description: Category: Unreleased Structures

2019-05-01T06:58:41Z

New page: '''Unreleased structure''' The entry 6jx6 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6jx6 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]