4ggf - Revision history

OCA at 15:46, 14 March 2024

OCA — Thu, 14 Mar 2024 15:46:04 GMT

←Older revision		Revision as of 15:46, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ggf]] is a 8 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=4GGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GGF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ggf]] is a 8 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=4GGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GGF 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.6Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [https://pdbe.org/4ggf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [https://www.ebi.ac.uk/pdbsum/4ggf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggf 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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [https://pdbe.org/4ggf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [https://www.ebi.ac.uk/pdbsum/4ggf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/S10A8_HUMAN S10A8_HUMAN] S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:12626582</ref> <ref>PMID:15331440</ref> <ref>PMID:15598812</ref> <ref>PMID:15642721</ref> <ref>PMID:16258195</ref> <ref>PMID:19087201</ref> <ref>PMID:19122197</ref> <ref>PMID:19935772</ref> <ref>PMID:21487906</ref> <ref>PMID:22808130</ref> <ref>PMID:22363402</ref>		[https://www.uniprot.org/uniprot/S10A8_HUMAN S10A8_HUMAN] S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:12626582</ref> <ref>PMID:15331440</ref> <ref>PMID:15598812</ref> <ref>PMID:15642721</ref> <ref>PMID:16258195</ref> <ref>PMID:19087201</ref> <ref>PMID:19122197</ref> <ref>PMID:19935772</ref> <ref>PMID:21487906</ref> <ref>PMID:22808130</ref> <ref>PMID:22363402</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn(2+) sequestration. The asymmetry of the CP heterodimer creates a single Mn(2+)-binding site from six histidine residues, which distinguishes CP from all other Mn(2+)-binding proteins. Analysis of CP mutants with altered metal-binding properties revealed that, despite both Mn(2+) and Zn(2+) being essential metals, maximal growth inhibition of multiple bacterial pathogens requires Mn(2+) sequestration. These data establish the importance of Mn(2+) sequestration in defense against infection, explain the broad-spectrum antimicrobial activity of CP relative to other S100 proteins, and clarify the impact of metal depletion on the innate immune response to infection.
-
-	Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.,Damo SM, Kehl-Fie TE, Sugitani N, Holt ME, Rathi S, Murphy WJ, Zhang Y, Betz C, Hench L, Fritz G, Skaar EP, Chazin WJ Proc Natl Acad Sci U S A. 2013 Feb 19. PMID:23431180<ref>PMID:23431180</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4ggf" style="background-color:#fffaf0;"></div>

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

OCA at 06:55, 26 October 2022

OCA — Wed, 26 Oct 2022 06:55:17 GMT

←Older revision		Revision as of 06:55, 26 October 2022
Line 1:		Line 1:

	==Crystal structure of Mn2+ bound calprotectin==		==Crystal structure of Mn2+ bound calprotectin==
-	<StructureSection load='4ggf' size='340' side='right' caption='[[4ggf]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='4ggf' size='340' side='right'caption='[[4ggf]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ggf]] is a 8 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=4GGF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4GGF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ggf]] is a 8 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=4GGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GGF 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100A8, CAGA, CFAG, MRP8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), S100A9, CAGB, CFAG, MRP14 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [https://pdbe.org/4ggf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [https://www.ebi.ac.uk/pdbsum/4ggf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggf 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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [~~http~~://pdbe.org/4ggf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ggf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggf ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/S10A8_HUMAN S10A8_HUMAN]] S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:12626582</ref> <ref>PMID:15331440</ref> <ref>PMID:15598812</ref> <ref>PMID:15642721</ref> <ref>PMID:16258195</ref> <ref>PMID:19087201</ref> <ref>PMID:19122197</ref> <ref>PMID:19935772</ref> <ref>PMID:21487906</ref> <ref>PMID:22808130</ref> <ref>PMID:22363402</ref> [[http://www.uniprot.org/uniprot/S10A9_HUMAN S10A9_HUMAN]] S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:8423249</ref> <ref>PMID:12626582</ref> <ref>PMID:15331440</ref> <ref>PMID:15598812</ref> <ref>PMID:15642721</ref> <ref>PMID:16258195</ref> <ref>PMID:19534726</ref> <ref>PMID:19087201</ref> <ref>PMID:19122197</ref> <ref>PMID:19402754</ref> <ref>PMID:19935772</ref> <ref>PMID:20103766</ref> <ref>PMID:21325622</ref> <ref>PMID:22804476</ref> <ref>PMID:21487906</ref> <ref>PMID:22808130</ref> <ref>PMID:22363402</ref>	+	[https://www.uniprot.org/uniprot/S10A8_HUMAN S10A8_HUMAN] S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:12626582</ref> <ref>PMID:15331440</ref> <ref>PMID:15598812</ref> <ref>PMID:15642721</ref> <ref>PMID:16258195</ref> <ref>PMID:19087201</ref> <ref>PMID:19122197</ref> <ref>PMID:19935772</ref> <ref>PMID:21487906</ref> <ref>PMID:22808130</ref> <ref>PMID:22363402</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:

	==See Also==		==See Also==
-	*[[S100 ~~protein~~\|S100 ~~protein~~]]	+	*[[S100 proteins 3D structures\|S100 proteins 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Damo, S M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Fritz, G~~]]	+	[[Category: Damo SM]]
-	[[Category: ~~Antimicrobial protein]]~~	+	[[Category: Fritz G]]
-	~~[[Category: Ef-hand]]~~	+
-	~~[[Category: S100~~]]	+

OCA at 16:45, 5 August 2016

OCA — Fri, 05 Aug 2016 16:45:27 GMT

←Older revision		Revision as of 16:45, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of Mn2+ bound calprotectin==		==Crystal structure of Mn2+ bound calprotectin==
	<StructureSection load='4ggf' size='340' side='right' caption='[[4ggf]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4ggf' size='340' side='right' caption='[[4ggf]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ggf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GGF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ggf]] is a 8 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=4GGF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GGF 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100A8, CAGA, CFAG, MRP8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), S100A9, CAGB, CFAG, MRP14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100A8, CAGA, CFAG, MRP8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), S100A9, CAGB, CFAG, MRP14 ([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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [http://www.ebi.ac.uk/pdbsum/4ggf 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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [http://pdbe.org/4ggf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [http://www.ebi.ac.uk/pdbsum/4ggf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4ggf" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Damo, S M]]		[[Category: Damo, S M]]
	[[Category: Fritz, G]]		[[Category: Fritz, G]]

OCA at 04:07, 25 December 2014

OCA — Thu, 25 Dec 2014 04:07:31 GMT

←Older revision		Revision as of 04:07, 25 December 2014
Line 7:		Line 7:
	<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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [http://www.ebi.ac.uk/pdbsum/4ggf 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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [http://www.ebi.ac.uk/pdbsum/4ggf PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/S10A8_HUMAN S10A8_HUMAN]] S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:12626582</ref> <ref>PMID:15331440</ref> <ref>PMID:15598812</ref> <ref>PMID:15642721</ref> <ref>PMID:16258195</ref> <ref>PMID:19087201</ref> <ref>PMID:19122197</ref> <ref>PMID:19935772</ref> <ref>PMID:21487906</ref> <ref>PMID:22808130</ref> <ref>PMID:22363402</ref> [[http://www.uniprot.org/uniprot/S10A9_HUMAN S10A9_HUMAN]] S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:8423249</ref> <ref>PMID:12626582</ref> <ref>PMID:15331440</ref> <ref>PMID:15598812</ref> <ref>PMID:15642721</ref> <ref>PMID:16258195</ref> <ref>PMID:19534726</ref> <ref>PMID:19087201</ref> <ref>PMID:19122197</ref> <ref>PMID:19402754</ref> <ref>PMID:19935772</ref> <ref>PMID:20103766</ref> <ref>PMID:21325622</ref> <ref>PMID:22804476</ref> <ref>PMID:21487906</ref> <ref>PMID:22808130</ref> <ref>PMID:22363402</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:46, 21 December 2014

OCA — Sun, 21 Dec 2014 11:46:36 GMT

←Older revision		Revision as of 11:46, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4ggf\| PDB~~=4ggf \| ~~SCENE~~= }}	+	==Crystal structure of Mn2+ bound calprotectin==
-	===~~Crystal~~ structure ~~of Mn2~~+ ~~bound calprotectin~~===	+	<StructureSection load='4ggf' size='340' side='right' caption='[[4ggf]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23431180}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ggf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GGF 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">S100A8, CAGA, CFAG, MRP8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), S100A9, CAGB, CFAG, MRP14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4ggf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ggf RCSB], [http://www.ebi.ac.uk/pdbsum/4ggf PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn(2+) sequestration. The asymmetry of the CP heterodimer creates a single Mn(2+)-binding site from six histidine residues, which distinguishes CP from all other Mn(2+)-binding proteins. Analysis of CP mutants with altered metal-binding properties revealed that, despite both Mn(2+) and Zn(2+) being essential metals, maximal growth inhibition of multiple bacterial pathogens requires Mn(2+) sequestration. These data establish the importance of Mn(2+) sequestration in defense against infection, explain the broad-spectrum antimicrobial activity of CP relative to other S100 proteins, and clarify the impact of metal depletion on the innate immune response to infection.

-	~~==Function==~~	+	Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.,Damo SM, Kehl-Fie TE, Sugitani N, Holt ME, Rathi S, Murphy WJ, Zhang Y, Betz C, Hench L, Fritz G, Skaar EP, Chazin WJ Proc Natl Acad Sci U S A. 2013 Feb 19. PMID:23431180<ref>PMID:23431180</ref>
-	~~[[http://www.uniprot.org/uniprot/S10A8_HUMAN S10A8_HUMAN]] S100A8 is a calcium-~~ and ~~zinc-binding protein which plays a prominent role~~ in the ~~regulation of inflammatory processes and~~ immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to ~~NCF2/P67PHOX~~. ~~The extracellular functions involve proinfammatory~~, ~~antimicrobial~~, ~~oxidant~~-~~scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes~~, ~~promotion of cytokine and chemokine production~~, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:12626582</ref><ref>PMID:15331440</ref><ref>PMID:15598812</ref><ref>PMID:15642721</ref><ref>PMID:16258195</ref><ref>PMID:19087201</ref><ref>PMID:19122197</ref><ref>PMID:19935772</ref><ref>PMID:21487906</ref><ref>PMID:22808130</ref><ref>PMID:22363402</ref> [[http://www.uniprot.org/uniprot/S10A9_HUMAN S10A9_HUMAN]] S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, ~~adhesion~~, ~~can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK~~, ~~PI3K/AKT~~, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, ~~transfering arachidonic acid~~, ~~an essential cofactor~~, ~~to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX~~. ~~The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities~~. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:8423249</ref><ref>PMID:12626582</ref><ref>PMID:15331440</ref><ref>PMID:15598812</ref><ref>PMID:15642721</ref><ref>PMID:16258195</ref><ref>PMID:19534726</ref><ref>PMID:19087201</ref><ref>PMID:19122197</ref><ref>PMID:19402754</ref><ref>PMID:19935772</ref><ref>PMID:20103766</ref><ref>PMID:21325622</ref><ref>PMID:22804476</ref><ref>PMID:21487906</ref><ref>PMID:22808130</ref><ref>PMID:~~22363402~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4ggf]] is~~ a ~~8 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4GGF OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	<references ~~group="xtra"~~/><~~references~~/>	+	*[[S100 protein\|S100 protein]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Damo, S M.]]	+	[[Category: Damo, S M]]
-	[[Category: Fritz, G.]]	+	[[Category: Fritz, G]]
	[[Category: Antimicrobial protein]]		[[Category: Antimicrobial protein]]
	[[Category: Ef-hand]]		[[Category: Ef-hand]]
	[[Category: S100]]		[[Category: S100]]

OCA at 07:46, 27 March 2013

OCA — Wed, 27 Mar 2013 07:46:29 GMT

←Older revision		Revision as of 07:46, 27 March 2013
Line 1:		Line 1:
-	[[Image:4ggf.png\|left\|200px]]
-
	{{STRUCTURE_4ggf\| PDB=4ggf \| SCENE= }}		{{STRUCTURE_4ggf\| PDB=4ggf \| SCENE= }}
-
	===Crystal structure of Mn2+ bound calprotectin===		===Crystal structure of Mn2+ bound calprotectin===
-
	{{ABSTRACT_PUBMED_23431180}}		{{ABSTRACT_PUBMED_23431180}}
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/S10A8_HUMAN S10A8_HUMAN]] S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:12626582</ref><ref>PMID:15331440</ref><ref>PMID:15598812</ref><ref>PMID:15642721</ref><ref>PMID:16258195</ref><ref>PMID:19087201</ref><ref>PMID:19122197</ref><ref>PMID:19935772</ref><ref>PMID:21487906</ref><ref>PMID:22808130</ref><ref>PMID:22363402</ref> [[http://www.uniprot.org/uniprot/S10A9_HUMAN S10A9_HUMAN]] S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread.<ref>PMID:8423249</ref><ref>PMID:12626582</ref><ref>PMID:15331440</ref><ref>PMID:15598812</ref><ref>PMID:15642721</ref><ref>PMID:16258195</ref><ref>PMID:19534726</ref><ref>PMID:19087201</ref><ref>PMID:19122197</ref><ref>PMID:19402754</ref><ref>PMID:19935772</ref><ref>PMID:20103766</ref><ref>PMID:21325622</ref><ref>PMID:22804476</ref><ref>PMID:21487906</ref><ref>PMID:22808130</ref><ref>PMID:22363402</ref>

	==About this Structure==		==About this Structure==
	[[4ggf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGF OCA].		[[4ggf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGF OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Damo, S M.]]		[[Category: Damo, S M.]]

OCA at 13:19, 6 March 2013

OCA — Wed, 06 Mar 2013 13:19:29 GMT

←Older revision		Revision as of 13:19, 6 March 2013
Line 1:		Line 1:
-	[[Image:4ggf.~~jpg~~\|left\|200px]]	+	[[Image:4ggf.png\|left\|200px]]

	{{STRUCTURE_4ggf\| PDB=4ggf \| SCENE= }}		{{STRUCTURE_4ggf\| PDB=4ggf \| SCENE= }}
Line 5:		Line 5:
	===Crystal structure of Mn2+ bound calprotectin===		===Crystal structure of Mn2+ bound calprotectin===

		+	{{ABSTRACT_PUBMED_23431180}}

	==About this Structure==		==About this Structure==

OCA at 13:58, 20 February 2013

OCA — Wed, 20 Feb 2013 13:58:37 GMT

←Older revision		Revision as of 13:58, 20 February 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4ggf.jpg\|left\|200px]]

-	~~The entry~~ 4ggf ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4ggf\| PDB=4ggf \| SCENE= }}

-	~~Authors: Damo, S.M., Fritz, G.~~	+	===Crystal structure of Mn2+ bound calprotectin===

-	~~Description: Crystal~~ structure ~~of Mn2+ bound calprotectin~~	+
		+	==About this Structure==
		+	[[4ggf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGF OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Damo, S M.]]
		+	[[Category: Fritz, G.]]
		+	[[Category: Antimicrobial protein]]
		+	[[Category: Ef-hand]]
		+	[[Category: S100]]

OCA at 08:34, 31 October 2012

OCA — Wed, 31 Oct 2012 08:34:13 GMT

←Older revision		Revision as of 08:34, 31 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ggf is ON HOLD	+	The entry 4ggf is ON HOLD until Paper Publication

	Authors: Damo, S.M., Fritz, G.		Authors: Damo, S.M., Fritz, G.

	Description: Crystal structure of Mn2+ bound calprotectin		Description: Crystal structure of Mn2+ bound calprotectin

OCA: Protected "4ggf" [edit=sysop:move=sysop]

OCA — Wed, 15 Aug 2012 05:25:41 GMT

Protected "4ggf" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:25, 15 August 2012