6xq3 - Revision history

OCA at 14:58, 18 October 2023

OCA — Wed, 18 Oct 2023 14:58:51 GMT

←Older revision		Revision as of 14:58, 18 October 2023
Line 3:		Line 3:
	<StructureSection load='6xq3' size='340' side='right'caption='[[6xq3]], [[Resolution\|resolution]] 1.71Å' scene=''>		<StructureSection load='6xq3' size='340' side='right'caption='[[6xq3]], [[Resolution\|resolution]] 1.71Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6xq3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XQ3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xq3]] 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=6XQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XQ3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=V6Y:3-(3-{[3-(4-carboxyphenoxy)phenyl]methoxy}phenyl)-1H-indole-2-carboxylic+acid'>V6Y</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]] 1.71Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6xq1\|6xq1]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=V6Y:3-(3-{[3-(4-carboxyphenoxy)phenyl]methoxy}phenyl)-1H-indole-2-carboxylic+acid'>V6Y</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGER, RAGE ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6xq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xq3 OCA], [https://pdbe.org/6xq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xq3 RCSB], [https://www.ebi.ac.uk/pdbsum/6xq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xq3 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=6xq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xq3 OCA], [https://pdbe.org/6xq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xq3 RCSB], [https://www.ebi.ac.uk/pdbsum/6xq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xq3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/RAGE_HUMAN RAGE_HUMAN]] Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.<ref>PMID:19906677</ref>	+	[https://www.uniprot.org/uniprot/RAGE_HUMAN RAGE_HUMAN] Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.<ref>PMID:19906677</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chazin~~, W J~~]]	+	[[Category: Chazin WJ]]
-	[[Category: Christov~~, P P~~]]	+	[[Category: Christov PP]]
-	[[Category: Gilston~~, B A~~]]	+	[[Category: Gilston BA]]
-	[[Category: Gogliotti~~, R D~~]]	+	[[Category: Gogliotti RD]]
-	[[Category: Kim, K]]	+	[[Category: Kim K]]
-	[[Category: Kozlyuk, N]]	+	[[Category: Kozlyuk N]]
-	[[Category: Ovee, M]]	+	[[Category: Ovee M]]
-	[[Category: Salay~~, L E~~]]	+	[[Category: Salay LE]]
-	[[Category: Waterson~~, A G]]~~	+	[[Category: Waterson AG]]
-	~~[[Category: Advanced glycation end product]]~~	+
-	~~[[Category: Ig-like domain]]~~	+
-	~~[[Category: Rage]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 10:42, 28 July 2021

OCA — Wed, 28 Jul 2021 10:42:17 GMT

←Older revision		Revision as of 10:42, 28 July 2021
Line 1:		Line 1:

	==Receptor for Advanced Glycation End Products VC1 domain in complex with 3-(3-(((3-(4-Carboxyphenoxy)benzyl)oxy)methyl)phenyl)-1H-indole-2-carboxylic acid==		==Receptor for Advanced Glycation End Products VC1 domain in complex with 3-(3-(((3-(4-Carboxyphenoxy)benzyl)oxy)methyl)phenyl)-1H-indole-2-carboxylic acid==
-	<StructureSection load='6xq3' size='340' side='right'caption='[[6xq3]]' scene=''>	+	<StructureSection load='6xq3' size='340' side='right'caption='[[6xq3]], [[Resolution\|resolution]] 1.71Å' 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=6XQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XQ3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xq3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XQ3 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=6xq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xq3 OCA], [https://pdbe.org/6xq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xq3 RCSB], [https://www.ebi.ac.uk/pdbsum/6xq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xq3 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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=V6Y:3-(3-{[3-(4-carboxyphenoxy)phenyl]methoxy}phenyl)-1H-indole-2-carboxylic+acid'>V6Y</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6xq1\|6xq1]]</div></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AGER, RAGE ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6xq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xq3 OCA], [https://pdbe.org/6xq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xq3 RCSB], [https://www.ebi.ac.uk/pdbsum/6xq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xq3 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/RAGE_HUMAN RAGE_HUMAN]] Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.<ref>PMID:19906677</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Receptor for Advanced Glycation End products (RAGE) is a pattern recognition receptor that signals for inflammation via the NF-kappaB pathway. RAGE has been pursued as a potential target to suppress symptoms of diabetes and is of interest in a number of other diseases associated with chronic inflammation, such as inflammatory bowel disease and bronchopulmonary dysplasia. Screening and optimization have previously produced small molecules that inhibit the activity of RAGE in cell-based assays, but efforts to develop a therapeutically viable direct-binding RAGE inhibitor have yet to be successful. Here, we show that a fragment-based approach can be applied to discover fundamentally new types of RAGE inhibitors that specifically target the ligand-binding surface. A series of systematic assays of structural stability, solubility, and crystallization were performed to select constructs of the RAGE ligand-binding domain and optimize conditions for NMR-based screening and co-crystallization of RAGE with hit fragments. An NMR-based screen of a highly curated ~14 000-member fragment library produced 21 fragment leads. Of these, three were selected for elaboration based on structure-activity relationships generated through cycles of structural analysis by X-ray crystallography, structure-guided design principles, and synthetic chemistry. These results, combined with crystal structures of the first linked fragment compounds, demonstrate the applicability of the fragment-based approach to the discovery of RAGE inhibitors.
		+
		+	A fragment-based approach to discovery of Receptor for Advanced Glycation End products inhibitors.,Kozlyuk N, Gilston BA, Salay LE, Gogliotti RD, Christov PP, Kim K, Ovee M, Waterson AG, Chazin WJ Proteins. 2021 Jun 22. doi: 10.1002/prot.26162. PMID:34156100<ref>PMID:34156100</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xq3" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chazin WJ]]	+	[[Category: Chazin, W J]]
-	[[Category: Christov PP]]	+	[[Category: Christov, P P]]
-	[[Category: Gilston BA]]	+	[[Category: Gilston, B A]]
-	[[Category: Gogliotti RD]]	+	[[Category: Gogliotti, R D]]
-	[[Category: Kim K]]	+	[[Category: Kim, K]]
-	[[Category: Kozlyuk N]]	+	[[Category: Kozlyuk, N]]
-	[[Category: Ovee M]]	+	[[Category: Ovee, M]]
-	[[Category: Salay LE]]	+	[[Category: Salay, L E]]
-	[[Category: Waterson AG]]	+	[[Category: Waterson, A G]]
		+	[[Category: Advanced glycation end product]]
		+	[[Category: Ig-like domain]]
		+	[[Category: Rage]]
		+	[[Category: Receptor]]
		+	[[Category: Signaling protein]]

OCA at 09:50, 14 July 2021

OCA — Wed, 14 Jul 2021 09:50:01 GMT

←Older revision		Revision as of 09:50, 14 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6xq3 is ON HOLD until Paper Publication~~	+	==Receptor for Advanced Glycation End Products VC1 domain in complex with 3-(3-(((3-(4-Carboxyphenoxy)benzyl)oxy)methyl)phenyl)-1H-indole-2-carboxylic acid==
-		+	<StructureSection load='6xq3' size='340' side='right'caption='[[6xq3]]' scene=''>
-	~~Authors: Salay, L.E., Kozlyuk, N., Gilston, B.A., Gogliotti, R.D., Christov, P.P., Kim, K., Ovee, M., Waterson, A.G., Chazin, W.J.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XQ3 FirstGlance]. <br>
-	~~Description:~~ Receptor for Advanced Glycation End Products VC1 domain in complex with 3-(3-(((3-(4-Carboxyphenoxy)benzyl)oxy)methyl)phenyl)-1H-indole-2-carboxylic acid	+	</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=6xq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xq3 OCA], [https://pdbe.org/6xq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xq3 RCSB], [https://www.ebi.ac.uk/pdbsum/6xq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xq3 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Chazin~~, W.J~~]]	+	__TOC__
-	[[Category: Christov~~, P.P~~]]	+	</StructureSection>
-	[[Category: ~~Ovee, M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Waterson, A.G~~]]	+	[[Category: Chazin WJ]]
-	[[Category: Kim, K]]	+	[[Category: Christov PP]]
-	[[Category: Kozlyuk, N]]	+	[[Category: Gilston BA]]
-	[[Category: ~~Salay, L.E~~]]	+	[[Category: Gogliotti RD]]
-	[[Category: ~~Gogliotti, R.D~~]]	+	[[Category: Kim K]]
-	[[Category: ~~Gilston, B.A~~]]	+	[[Category: Kozlyuk N]]
		+	[[Category: Ovee M]]
		+	[[Category: Salay LE]]
		+	[[Category: Waterson AG]]

OCA at 03:52, 5 August 2020

OCA — Wed, 05 Aug 2020 03:52:09 GMT

←Older revision		Revision as of 03:52, 5 August 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6xq3 is ON HOLD	+	The entry 6xq3 is ON HOLD until Paper Publication

	Authors: Salay, L.E., Kozlyuk, N., Gilston, B.A., Gogliotti, R.D., Christov, P.P., Kim, K., Ovee, M., Waterson, A.G., Chazin, W.J.		Authors: Salay, L.E., Kozlyuk, N., Gilston, B.A., Gogliotti, R.D., Christov, P.P., Kim, K., Ovee, M., Waterson, A.G., Chazin, W.J.

OCA: Protected "6xq3" [edit=sysop:move=sysop]

OCA — Wed, 22 Jul 2020 06:52:28 GMT

Protected "6xq3" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:52, 22 July 2020

OCA: New page: '''Unreleased structure''' The entry 6xq3 is ON HOLD Authors: Salay, L.E., Kozlyuk, N., Gilston, B.A., Gogliotti, R.D., Christov, P.P., Kim, K., Ovee, M., Waterson, A.G., Chazin, W.J. ...

OCA — Wed, 22 Jul 2020 06:52:27 GMT

New page: '''Unreleased structure''' The entry 6xq3 is ON HOLD Authors: Salay, L.E., Kozlyuk, N., Gilston, B.A., Gogliotti, R.D., Christov, P.P., Kim, K., Ovee, M., Waterson, A.G., Chazin, W.J. ...

New page

'''Unreleased structure'''

The entry 6xq3 is ON HOLD

Authors: Salay, L.E., Kozlyuk, N., Gilston, B.A., Gogliotti, R.D., Christov, P.P., Kim, K., Ovee, M., Waterson, A.G., Chazin, W.J.

Description: Receptor for Advanced Glycation End Products VC1 domain in complex with 3-(3-(((3-(4-Carboxyphenoxy)benzyl)oxy)methyl)phenyl)-1H-indole-2-carboxylic acid
[[Category: Unreleased Structures]]
[[Category: Chazin, W.J]]
[[Category: Christov, P.P]]
[[Category: Ovee, M]]
[[Category: Waterson, A.G]]
[[Category: Kim, K]]
[[Category: Kozlyuk, N]]
[[Category: Salay, L.E]]
[[Category: Gogliotti, R.D]]
[[Category: Gilston, B.A]]