6afe - Revision history

OCA at 09:28, 22 November 2023

2023-11-22T09:28:50Z

←Older revision		Revision as of 09:28, 22 November 2023
Line 1:		Line 1:

	==DJ-1 with compound 7==		==DJ-1 with compound 7==
-	<StructureSection load='6afe' size='340' side='right' caption='[[6afe]], [[Resolution\|resolution]] 1.50Å' scene=''>	+	<StructureSection load='6afe' size='340' side='right'caption='[[6afe]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6afe]] 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=6AFE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AFE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6afe]] is a 1 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=6AFE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AFE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=72T:7-(trifluoromethyl)-1~{H}-indole-2,3-dione'>72T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.5Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PARK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=72T:7-(trifluoromethyl)-1~{H}-indole-2,3-dione'>72T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=6afe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6afe OCA], [~~http~~://pdbe.org/6afe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6afe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6afe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6afe 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=6afe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6afe OCA], [https://pdbe.org/6afe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6afe RCSB], [https://www.ebi.ac.uk/pdbsum/6afe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6afe ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN]] Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:[~~http~~://omim.org/entry/606324 606324]]. A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).<ref>PMID:12851414</ref> <ref>PMID:12446870</ref> <ref>PMID:14713311</ref> <ref>PMID:12953260</ref> <ref>PMID:15365989</ref> <ref>PMID:14607841</ref> <ref>PMID:15254937</ref> <ref>PMID:17846173</ref>	+	[https://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN] Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:[https://omim.org/entry/606324 606324]. A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).<ref>PMID:12851414</ref> <ref>PMID:12446870</ref> <ref>PMID:14713311</ref> <ref>PMID:12953260</ref> <ref>PMID:15365989</ref> <ref>PMID:14607841</ref> <ref>PMID:15254937</ref> <ref>PMID:17846173</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN]] Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone.<ref>PMID:9070310</ref> <ref>PMID:11477070</ref> <ref>PMID:12612053</ref> <ref>PMID:14749723</ref> <ref>PMID:15502874</ref> <ref>PMID:15976810</ref> <ref>PMID:16390825</ref> <ref>PMID:17015834</ref> <ref>PMID:18626009</ref> <ref>PMID:18711745</ref> <ref>PMID:20304780</ref> <ref>PMID:21097510</ref> <ref>PMID:12939276</ref> <ref>PMID:15181200</ref>	+	[https://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN] Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone.<ref>PMID:9070310</ref> <ref>PMID:11477070</ref> <ref>PMID:12612053</ref> <ref>PMID:14749723</ref> <ref>PMID:15502874</ref> <ref>PMID:15976810</ref> <ref>PMID:16390825</ref> <ref>PMID:17015834</ref> <ref>PMID:18626009</ref> <ref>PMID:18711745</ref> <ref>PMID:20304780</ref> <ref>PMID:21097510</ref> <ref>PMID:12939276</ref> <ref>PMID:15181200</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6afe" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6afe" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Protein DJ-1\|Protein DJ-1]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Caaveiro, J M.M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Tashiro, S~~]]	+	[[Category: Caaveiro JMM]]
-	[[Category: ~~Tsumoto, K~~]]	+	[[Category: Tashiro S]]
-	[[Category: ~~Dj-1]]~~	+	[[Category: Tsumoto K]]
-	~~[[Category: Drug discovery]]~~	+
-	~~[[Category: Fragment-based drug discovery]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Parkinson's disease~~]]	+

OCA at 08:39, 3 October 2018

2018-10-03T08:39:15Z

←Older revision		Revision as of 08:39, 3 October 2018
Line 3:		Line 3:
	<StructureSection load='6afe' size='340' side='right' caption='[[6afe]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='6afe' size='340' side='right' caption='[[6afe]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6afe]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AFE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6afe]] 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=6AFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AFE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=72T:7-(trifluoromethyl)-1~{H}-indole-2,3-dione'>72T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=72T:7-(trifluoromethyl)-1~{H}-indole-2,3-dione'>72T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PARK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6afe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6afe OCA], [http://pdbe.org/6afe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6afe RCSB], [http://www.ebi.ac.uk/pdbsum/6afe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6afe 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=6afe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6afe OCA], [http://pdbe.org/6afe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6afe RCSB], [http://www.ebi.ac.uk/pdbsum/6afe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6afe ProSAT]</span></td></tr>
	</table>		</table>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Caaveiro, J M.M]]		[[Category: Caaveiro, J M.M]]
	[[Category: Tashiro, S]]		[[Category: Tashiro, S]]

OCA at 07:23, 29 August 2018

2018-08-29T07:23:59Z

←Older revision		Revision as of 07:23, 29 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6afe is ~~ON HOLD~~	+	==DJ-1 with compound 7==
		+	<StructureSection load='6afe' size='340' side='right' caption='[[6afe]], [[Resolution\|resolution]] 1.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6afe]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AFE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=72T:7-(trifluoromethyl)-1~{H}-indole-2,3-dione'>72T</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=6afe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6afe OCA], [http://pdbe.org/6afe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6afe RCSB], [http://www.ebi.ac.uk/pdbsum/6afe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6afe ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN]] Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:[http://omim.org/entry/606324 606324]]. A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).<ref>PMID:12851414</ref> <ref>PMID:12446870</ref> <ref>PMID:14713311</ref> <ref>PMID:12953260</ref> <ref>PMID:15365989</ref> <ref>PMID:14607841</ref> <ref>PMID:15254937</ref> <ref>PMID:17846173</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN]] Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone.<ref>PMID:9070310</ref> <ref>PMID:11477070</ref> <ref>PMID:12612053</ref> <ref>PMID:14749723</ref> <ref>PMID:15502874</ref> <ref>PMID:15976810</ref> <ref>PMID:16390825</ref> <ref>PMID:17015834</ref> <ref>PMID:18626009</ref> <ref>PMID:18711745</ref> <ref>PMID:20304780</ref> <ref>PMID:21097510</ref> <ref>PMID:12939276</ref> <ref>PMID:15181200</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DJ-1 is a Parkinson's disease associated protein endowed with enzymatic, redox sensing, regulatory, chaperoning, and neuroprotective activities. Although DJ-1 has been vigorously studied for the past decade and a half, its exact role in the progression of the disease remains uncertain. In addition, little is known about the spatiotemporal regulation of DJ-1, or the biochemical basis explaining its numerous biological functions. Progress has been hampered by the lack of inhibitors with precisely known mechanisms of action. Herein, we have employed biophysical methodologies and X-ray crystallography to identify and to optimize a family of compounds inactivating the critical Cys106 residue of human DJ-1. We demonstrate these compounds are potent inhibitors of various activities of DJ-1 in vitro and in cell-based assays. This study reports a new family of DJ-1 inhibitors with a defined mechanism of action, and contributes toward the understanding of the biological function of DJ-1.

-	~~Authors:~~ Caaveiro, J.M~~.M.~~, ~~Tashiro~~, S., ~~Tsumoto~~, K.	+	Discovery and Optimization of Inhibitors of the Parkinson's Disease Associated Protein DJ-1.,Tashiro S, Caaveiro JMM, Nakakido M, Tanabe A, Nagatoishi S, Tamura Y, Matsuda N, Liu D, Hoang QQ, Tsumoto K ACS Chem Biol. 2018 Aug 15. doi: 10.1021/acschembio.8b00701. PMID:30063823<ref>PMID:30063823</ref>

-	~~Description: DJ-1 with compound 7~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Tsumoto, K]]~~	+	<div class="pdbe-citations 6afe" style="background-color:#fffaf0;"></div>
-	[[Category: Caaveiro, J.M.M]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Caaveiro, J M.M]]
	[[Category: Tashiro, S]]		[[Category: Tashiro, S]]
		+	[[Category: Tsumoto, K]]
		+	[[Category: Dj-1]]
		+	[[Category: Drug discovery]]
		+	[[Category: Fragment-based drug discovery]]
		+	[[Category: Hydrolase]]
		+	[[Category: Parkinson's disease]]

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

2018-08-15T14:40:24Z

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

←Older revision

Revision as of 14:40, 15 August 2018

OCA: New page: '''Unreleased structure''' The entry 6afe is ON HOLD Authors: Caaveiro, J.M.M., Tashiro, S., Tsumoto, K. Description: DJ-1 with compound 7 Category: Unreleased Structures [[Categor...

2018-08-15T14:40:22Z

New page: '''Unreleased structure''' The entry 6afe is ON HOLD Authors: Caaveiro, J.M.M., Tashiro, S., Tsumoto, K. Description: DJ-1 with compound 7 Category: Unreleased Structures [[Categor...

New page

'''Unreleased structure'''

The entry 6afe is ON HOLD

Authors: Caaveiro, J.M.M., Tashiro, S., Tsumoto, K.

Description: DJ-1 with compound 7
[[Category: Unreleased Structures]]
[[Category: Tsumoto, K]]
[[Category: Caaveiro, J.M.M]]
[[Category: Tashiro, S]]