3lk0 - Revision history

OCA at 09:46, 22 May 2024

OCA — Wed, 22 May 2024 09:46:18 GMT

←Older revision		Revision as of 09:46, 22 May 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>		[https://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	S100B is highly over-expressed in many cancers, including malignant melanoma. In such cancers, S100B binds wild-type p53 in a calcium-dependent manner, sequestering it, and promoting its degradation, resulting in the loss of p53-dependent tumor suppression activities. Therefore, S100B inhibitors may be able to restore wild-type p53 levels in certain cancers and provide a useful therapeutic strategy. In this regard, an automated and sensitive fluorescence polarization competition assay (FPCA) was developed and optimized to screen rapidly for lead compounds that bind Ca(2+)-loaded S100B and inhibit S100B target complex formation. A screen of 2000 compounds led to the identification of 26 putative S100B low molecular weight inhibitors. The binding of these small molecules to S100B was confirmed by nuclear magnetic resonance spectroscopy, and additional structural information was provided by x-ray crystal structures of several compounds in complexes with S100B. Notably, many of the identified inhibitors function by chemically modifying Cys84 in protein. These results validate the use of high-throughput FPCA to facilitate the identification of compounds that inhibit S100B. These lead compounds will be the subject of future optimization studies with the ultimate goal of developing a drug with therapeutic activity for the treatment of malignant melanoma and/or other cancers with elevated S100B.
		+
		+	In vitro screening and structural characterization of inhibitors of the S100B-p53 interaction.,Wilder PT, Charpentier TH, Liriano MA, Gianni K, Varney KM, Pozharski E, Coop A, Toth EA, Mackerell AD, Weber DJ Int J High Throughput Screen. 2010 Jul 7;2010(1):109-126. PMID:21132089<ref>PMID:21132089</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 3lk0" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:46, 7 February 2024

OCA — Wed, 07 Feb 2024 08:46:33 GMT

←Older revision		Revision as of 08:46, 7 February 2024
Line 3:		Line 3:
	<StructureSection load='3lk0' size='340' side='right'caption='[[3lk0]], [[Resolution\|resolution]] 2.04Å' scene=''>		<StructureSection load='3lk0' size='340' side='right'caption='[[3lk0]], [[Resolution\|resolution]] 2.04Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lk0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Bovin Bovin~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LK0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lk0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LK0 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>~~, ~~<scene name='pdbligand=Z80:3-(~~2~~-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</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]] 2.04Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[3lk1\|3lk1]]~~</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=Z80:3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">S100B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])~~</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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [https://pdbe.org/3lk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [https://www.ebi.ac.uk/pdbsum/3lk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lk0 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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [https://pdbe.org/3lk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [https://www.ebi.ac.uk/pdbsum/3lk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lk0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>	+	[https://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	S100B is highly over-expressed in many cancers, including malignant melanoma. In such cancers, S100B binds wild-type p53 in a calcium-dependent manner, sequestering it, and promoting its degradation, resulting in the loss of p53-dependent tumor suppression activities. Therefore, S100B inhibitors may be able to restore wild-type p53 levels in certain cancers and provide a useful therapeutic strategy. In this regard, an automated and sensitive fluorescence polarization competition assay (FPCA) was developed and optimized to screen rapidly for lead compounds that bind Ca(2+)-loaded S100B and inhibit S100B target complex formation. A screen of 2000 compounds led to the identification of 26 putative S100B low molecular weight inhibitors. The binding of these small molecules to S100B was confirmed by nuclear magnetic resonance spectroscopy, and additional structural information was provided by x-ray crystal structures of several compounds in complexes with S100B. Notably, many of the identified inhibitors function by chemically modifying Cys84 in protein. These results validate the use of high-throughput FPCA to facilitate the identification of compounds that inhibit S100B. These lead compounds will be the subject of future optimization studies with the ultimate goal of developing a drug with therapeutic activity for the treatment of malignant melanoma and/or other cancers with elevated S100B.	+
-		+
-	In vitro screening and structural characterization of inhibitors of the S100B-p53 interaction.,Wilder PT, Charpentier TH, Liriano MA, Gianni K, Varney KM, Pozharski E, Coop A, Toth EA, Mackerell AD, Weber DJ Int J High Throughput Screen. 2010 Jul 7;2010(1):109-126. PMID:21132089<ref>PMID:21132089</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3lk0" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bovin~~]]	+	[[Category: Bos taurus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Charpentier~~, T H~~]]	+	[[Category: Charpentier TH]]
-	[[Category: Weber~~, D J~~]]	+	[[Category: Weber DJ]]
-	[[Category: Wilder~~, P W]]~~	+	[[Category: Wilder PW]]
-	~~[[Category: Alpha helical]]~~	+
-	~~[[Category: Ef hand]]~~	+
-	~~[[Category: Metal binding protein]]~~	+
-	~~[[Category: Metal-binding~~]]	+

OCA at 13:40, 4 May 2022

OCA — Wed, 04 May 2022 13:40:54 GMT

←Older revision		Revision as of 13:40, 4 May 2022
Line 1:		Line 1:

	==X-ray structure of bovine SC0067,Ca(2+)-S100B==		==X-ray structure of bovine SC0067,Ca(2+)-S100B==
-	<StructureSection load='3lk0' size='340' side='right' caption='[[3lk0]], [[Resolution\|resolution]] 2.04Å' scene=''>	+	<StructureSection load='3lk0' size='340' side='right'caption='[[3lk0]], [[Resolution\|resolution]] 2.04Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lk0]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3LK0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lk0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LK0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=Z80:3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=Z80:3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3lk1\|3lk1]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3lk1\|3lk1]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100B ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [~~http~~://pdbe.org/3lk0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3lk0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3lk0 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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [https://pdbe.org/3lk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [https://www.ebi.ac.uk/pdbsum/3lk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lk0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>	+	[[https://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[S100 ~~protein~~\|S100 ~~protein~~]]	+	*[[S100 proteins 3D structures\|S100 proteins 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Bovin]]		[[Category: Bovin]]
		+	[[Category: Large Structures]]
	[[Category: Charpentier, T H]]		[[Category: Charpentier, T H]]
	[[Category: Weber, D J]]		[[Category: Weber, D J]]

OCA at 06:33, 4 April 2018

OCA — Wed, 04 Apr 2018 06:33:35 GMT

←Older revision		Revision as of 06:33, 4 April 2018
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3lk0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3lk0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[S100 protein\|S100 protein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:57, 1 November 2017

OCA — Wed, 01 Nov 2017 08:57:12 GMT

←Older revision		Revision as of 08:57, 1 November 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3lk0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3lk0" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[S100 protein\|S100 protein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:38, 5 August 2016

OCA — Fri, 05 Aug 2016 18:38:36 GMT

←Older revision		Revision as of 18:38, 5 August 2016
Line 1:		Line 1:
		+
	==X-ray structure of bovine SC0067,Ca(2+)-S100B==		==X-ray structure of bovine SC0067,Ca(2+)-S100B==
	<StructureSection load='3lk0' size='340' side='right' caption='[[3lk0]], [[Resolution\|resolution]] 2.04Å' scene=''>		<StructureSection load='3lk0' size='340' side='right' caption='[[3lk0]], [[Resolution\|resolution]] 2.04Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lk0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Bos_taurus Bos taurus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LK0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lk0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LK0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=Z80:3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=Z80:3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3lk1\|3lk1]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3lk1\|3lk1]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 ~~Bos taurus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [http://www.ebi.ac.uk/pdbsum/3lk0 PDBsum]</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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [http://pdbe.org/3lk0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [http://www.ebi.ac.uk/pdbsum/3lk0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lk0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3lk0" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bos taurus~~]]	+	[[Category: Bovin]]
	[[Category: Charpentier, T H]]		[[Category: Charpentier, T H]]
	[[Category: Weber, D J]]		[[Category: Weber, D J]]

OCA at 21:02, 25 December 2014

OCA — Thu, 25 Dec 2014 21:02:11 GMT

←Older revision		Revision as of 21:02, 25 December 2014
Line 8:		Line 8:
	<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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [http://www.ebi.ac.uk/pdbsum/3lk0 PDBsum]</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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [http://www.ebi.ac.uk/pdbsum/3lk0 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 15:03, 18 December 2014

OCA — Thu, 18 Dec 2014 15:03:13 GMT

←Older revision		Revision as of 15:03, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3lk0\| PDB=3lk0 \| SCENE= }}~~	+	==X-ray structure of bovine SC0067,Ca(2+)-S100B==
-	===X-ray structure of bovine SC0067,Ca(2+)-S100B===	+	<StructureSection load='3lk0' size='340' side='right' caption='[[3lk0]], [[Resolution\|resolution]] 2.04Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21132089}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3lk0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LK0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=Z80:3-(2-CHLORO-10H-PHENOTHIAZIN-10-YL)-N,N-DIMETHYLPROPAN-1-AMINE'>Z80</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3lk1\|3lk1]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus])</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=3lk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lk0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lk0 RCSB], [http://www.ebi.ac.uk/pdbsum/3lk0 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	S100B is highly over-expressed in many cancers, including malignant melanoma. In such cancers, S100B binds wild-type p53 in a calcium-dependent manner, sequestering it, and promoting its degradation, resulting in the loss of p53-dependent tumor suppression activities. Therefore, S100B inhibitors may be able to restore wild-type p53 levels in certain cancers and provide a useful therapeutic strategy. In this regard, an automated and sensitive fluorescence polarization competition assay (FPCA) was developed and optimized to screen rapidly for lead compounds that bind Ca(2+)-loaded S100B and inhibit S100B target complex formation. A screen of 2000 compounds led to the identification of 26 putative S100B low molecular weight inhibitors. The binding of these small molecules to S100B was confirmed by nuclear magnetic resonance spectroscopy, and additional structural information was provided by x-ray crystal structures of several compounds in complexes with S100B. Notably, many of the identified inhibitors function by chemically modifying Cys84 in protein. These results validate the use of high-throughput FPCA to facilitate the identification of compounds that inhibit S100B. These lead compounds will be the subject of future optimization studies with the ultimate goal of developing a drug with therapeutic activity for the treatment of malignant melanoma and/or other cancers with elevated S100B.

-	~~==Function==~~	+	In vitro screening and structural characterization of inhibitors of the S100B-p53 interaction.,Wilder PT, Charpentier TH, Liriano MA, Gianni K, Varney KM, Pozharski E, Coop A, Toth EA, Mackerell AD, Weber DJ Int J High Throughput Screen. 2010 Jul 7;2010(1):109-126. PMID:21132089<ref>PMID:21132089</ref>
-	[[http://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of ~~potassium ion antagonize~~ the ~~binding of both divalent cations, especially affecting high~~-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53~~/TP53 signaling~~. ~~Could assist ATAD3A cytoplasmic processing~~, ~~preventing aggregation and favoring mitochondrial localization~~ (~~By similarity~~).<ref>PMID:~~14661952~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3lk0]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Bos_taurus Bos taurus]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3LK0 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:021132089</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[S100 protein\|S100 protein]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
-	[[Category: Charpentier, T H.]]	+	[[Category: Charpentier, T H]]
-	[[Category: Weber, D J.]]	+	[[Category: Weber, D J]]
-	[[Category: Wilder, P W.]]	+	[[Category: Wilder, P W]]
	[[Category: Alpha helical]]		[[Category: Alpha helical]]
	[[Category: Ef hand]]		[[Category: Ef hand]]
	[[Category: Metal binding protein]]		[[Category: Metal binding protein]]
	[[Category: Metal-binding]]		[[Category: Metal-binding]]

OCA at 20:31, 4 April 2013

OCA — Thu, 04 Apr 2013 20:31:11 GMT

←Older revision		Revision as of 20:31, 4 April 2013
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-	[[Image:3lk0.jpg\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3lk0", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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	{{STRUCTURE_3lk0\| PDB=3lk0 \| SCENE= }}		{{STRUCTURE_3lk0\| PDB=3lk0 \| SCENE= }}
-
	===X-ray structure of bovine SC0067,Ca(2+)-S100B===		===X-ray structure of bovine SC0067,Ca(2+)-S100B===
		+	{{ABSTRACT_PUBMED_21132089}}

-		+	==Function==
-	~~<!--~~	+	[[http://www.uniprot.org/uniprot/S100B_BOVIN S100B_BOVIN]] Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity).<ref>PMID:14661952</ref>
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21132089}}, adds the Publication Abstract to the page~~	+
-	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov), where 21132089 is the PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_21132089}}~~	+

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~21132089~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021132089</ref><references group="xtra"/><references/>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Charpentier, T H.]]		[[Category: Charpentier, T H.]]

OCA: Protected "3lk0" [edit=sysop:move=sysop]

OCA — Wed, 29 Dec 2010 18:35:22 GMT

Protected "3lk0" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:35, 29 December 2010