3t4a - Revision history

OCA at 13:17, 14 March 2024

OCA — Thu, 14 Mar 2024 13:17:11 GMT

←Older revision		Revision as of 13:17, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3t4a' size='340' side='right'caption='[[3t4a]], [[Resolution\|resolution]] 3.40Å' scene=''>		<StructureSection load='3t4a' size='340' side='right'caption='[[3t4a]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t4a]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/~~Staam Staam~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t4a]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T4A FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[3t46\|3t46]], [[3t47\|3t47]], [[3t48\|3t48]], [[3t49\|3t49]]</div></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]] 3.4Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">SAV1159 ([https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=158878 STAAM])~~</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=3t4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4a OCA], [https://pdbe.org/3t4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t4a RCSB], [https://www.ebi.ac.uk/pdbsum/3t4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t4a 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=3t4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4a OCA], [https://pdbe.org/3t4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t4a RCSB], [https://www.ebi.ac.uk/pdbsum/3t4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t4a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[https://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[https://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[https://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>	+	[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[https://omim.org/entry/613779 613779]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[https://omim.org/entry/611378 611378]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[https://omim.org/entry/612925 612925]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>	+	[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	To survive in immune-competent hosts, the pathogen Staphylococcus aureus expresses and secretes a sophisticated array of proteins that inhibit the complement system. Among these are the staphylococcal complement inhibitors (SCIN), which are composed of three active proteins (SCIN-A, -B, and -C) and one purportedly inactive member (SCIN-D or ORF-D). Because previous work has focused almost exclusively on SCIN-A, we sought to provide initial structure/function information on additional SCIN proteins. To this end we determined crystal structures of an active, N-terminal truncation mutant of SCIN-B (denoted SCIN-B(18-85)) both free and bound to the C3c fragment of complement component C3 at 1.5 and 3.4 A resolution, respectively. Comparison of the C3c/SCIN-B(18-85) structure with that of C3c/SCIN-A revealed that both proteins target the same functional hotspot on the C3b/C3c surface yet harbor diversity in both the type of residues and interactions formed at their C3b/C3c interfaces. Most importantly, these structures allowed identification of Arg(44) and Tyr(51) as residues key for SCIN-B binding to C3b and subsequent inhibition of the AP C3 convertase. In addition, we also solved several crystal structures of SCIN-D to 1.3 A limiting resolution. This revealed an unexpected structural deviation in the N-terminal alpha helix relative to SCIN-A and SCIN-B. Comparative analysis of both electrostatic potentials and surface complementarity suggest a physical explanation for the inability of SCIN-D to bind C3b/C3c. Together, these studies provide a more thorough understanding of immune evasion by S. aureus and enhance potential use of SCIN proteins as templates for design of complement targeted therapeutics.	+
-		+
-	Diversity in the C3b Convertase Contact Residues and Tertiary Structures of the Staphylococcal Complement Inhibitor (SCIN) Protein Family.,Garcia BL, Summers BJ, Lin Z, Ramyar KX, Ricklin D, Kamath DV, Fu ZQ, Lambris JD, Geisbrecht BV J Biol Chem. 2012 Jan 2;287(1):628-40. Epub 2011 Nov 15. PMID:22086928<ref>PMID:22086928</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3t4a" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 31:		Line 21:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Staam~~]]	+	[[Category: Staphylococcus aureus subsp. aureus Mu50]]
-	[[Category: Garcia~~, B L~~]]	+	[[Category: Garcia BL]]
-	[[Category: Geisbrecht~~, B V~~]]	+	[[Category: Geisbrecht BV]]
-	[[Category: Summers~~, B J]]~~	+	[[Category: Summers BJ]]
-	~~[[Category: Age-related macular degeneration]]~~	+
-	~~[[Category: Cleavage on pair of basic residue]]~~	+
-	~~[[Category: Complement alternate pathway]]~~	+
-	~~[[Category: Complement pathway]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Disulfide bond]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Hemolytic uremic syndrome]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Immunity]]~~	+
-	~~[[Category: Inflammatory response]]~~	+
-	~~[[Category: Innate immunity]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Secreted]]~~	+
-	~~[[Category: Thioester bond~~]]	+

OCA at 16:42, 6 July 2022

OCA — Wed, 06 Jul 2022 16:42:24 GMT

←Older revision		Revision as of 16:42, 6 July 2022
Line 1:		Line 1:

	==Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution==		==Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution==
-	<StructureSection load='3t4a' size='340' side='right' caption='[[3t4a]], [[Resolution\|resolution]] 3.40Å' scene=''>	+	<StructureSection load='3t4a' size='340' side='right'caption='[[3t4a]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t4a]] is a 8 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [~~http~~://en.wikipedia.org/wiki/Staam Staam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3T4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t4a]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staam Staam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T4A FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t46\|3t46]], [[3t47\|3t47]], [[3t48\|3t48]], [[3t49\|3t49]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t46\|3t46]], [[3t47\|3t47]], [[3t48\|3t48]], [[3t49\|3t49]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SAV1159 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 STAAM])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SAV1159 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 STAAM])</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=3t4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4a OCA], [~~http~~://pdbe.org/3t4a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3t4a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3t4a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3t4a 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=3t4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4a OCA], [https://pdbe.org/3t4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t4a RCSB], [https://www.ebi.ac.uk/pdbsum/3t4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t4a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[~~http~~://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[~~http~~://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[~~http~~://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>	+	[[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[https://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[https://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[https://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>	+	[[https://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3t4a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3t4a" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Complement C3 3D structures\|Complement C3 3D structures]]
		+	*[[Fibrinogen binding protein\|Fibrinogen binding protein]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Staam]]		[[Category: Staam]]
	[[Category: Garcia, B L]]		[[Category: Garcia, B L]]

OCA at 09:47, 8 November 2017

OCA — Wed, 08 Nov 2017 09:47:59 GMT

←Older revision		Revision as of 09:47, 8 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 3t4a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3t4a" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Complement C3\|Complement C3]]
-	*[[Fibrinogen binding protein\|Fibrinogen binding protein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 22:14, 4 August 2016

OCA — Thu, 04 Aug 2016 22:14:22 GMT

←Older revision		Revision as of 22:14, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution==		==Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution==
	<StructureSection load='3t4a' size='340' side='right' caption='[[3t4a]], [[Resolution\|resolution]] 3.40Å' scene=''>		<StructureSection load='3t4a' size='340' side='right' caption='[[3t4a]], [[Resolution\|resolution]] 3.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/~~Staphylococcus_aureus_subsp._aureus_mu50 Staphylococcus aureus subsp. aureus mu50~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staam Staam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T4A FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t46\|3t46]], [[3t47\|3t47]], [[3t48\|3t48]], [[3t49\|3t49]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t46\|3t46]], [[3t47\|3t47]], [[3t48\|3t48]], [[3t49\|3t49]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SAV1159 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 ~~Staphylococcus aureus subsp. aureus Mu50~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SAV1159 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 STAAM])</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=3t4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t4a RCSB], [http://www.ebi.ac.uk/pdbsum/3t4a 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=3t4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4a OCA], [http://pdbe.org/3t4a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t4a RCSB], [http://www.ebi.ac.uk/pdbsum/3t4a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t4a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 3t4a" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: ~~Staphylococcus aureus subsp. aureus mu50~~]]	+	[[Category: Staam]]
	[[Category: Garcia, B L]]		[[Category: Garcia, B L]]
	[[Category: Geisbrecht, B V]]		[[Category: Geisbrecht, B V]]

OCA at 07:22, 21 December 2014

OCA — Sun, 21 Dec 2014 07:22:27 GMT

←Older revision		Revision as of 07:22, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3t4a\| PDB=3t4a \| SCENE= }}~~	+	==Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution==
-	===Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution===	+	<StructureSection load='3t4a' size='340' side='right' caption='[[3t4a]], [[Resolution\|resolution]] 3.40Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22086928}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_mu50 Staphylococcus aureus subsp. aureus mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T4A FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3t46\|3t46]], [[3t47\|3t47]], [[3t48\|3t48]], [[3t49\|3t49]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SAV1159 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 Staphylococcus aureus subsp. aureus Mu50])</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=3t4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t4a RCSB], [http://www.ebi.ac.uk/pdbsum/3t4a PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[http://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[http://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[http://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>		[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[http://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[http://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[http://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	To survive in immune-competent hosts, the pathogen Staphylococcus aureus expresses and secretes a sophisticated array of proteins that inhibit the complement system. Among these are the staphylococcal complement inhibitors (SCIN), which are composed of three active proteins (SCIN-A, -B, and -C) and one purportedly inactive member (SCIN-D or ORF-D). Because previous work has focused almost exclusively on SCIN-A, we sought to provide initial structure/function information on additional SCIN proteins. To this end we determined crystal structures of an active, N-terminal truncation mutant of SCIN-B (denoted SCIN-B(18-85)) both free and bound to the C3c fragment of complement component C3 at 1.5 and 3.4 A resolution, respectively. Comparison of the C3c/SCIN-B(18-85) structure with that of C3c/SCIN-A revealed that both proteins target the same functional hotspot on the C3b/C3c surface yet harbor diversity in both the type of residues and interactions formed at their C3b/C3c interfaces. Most importantly, these structures allowed identification of Arg(44) and Tyr(51) as residues key for SCIN-B binding to C3b and subsequent inhibition of the AP C3 convertase. In addition, we also solved several crystal structures of SCIN-D to 1.3 A limiting resolution. This revealed an unexpected structural deviation in the N-terminal alpha helix relative to SCIN-A and SCIN-B. Comparative analysis of both electrostatic potentials and surface complementarity suggest a physical explanation for the inability of SCIN-D to bind C3b/C3c. Together, these studies provide a more thorough understanding of immune evasion by S. aureus and enhance potential use of SCIN proteins as templates for design of complement targeted therapeutics.

-	~~==Function==~~	+	Diversity in the C3b Convertase Contact Residues and Tertiary Structures of the Staphylococcal Complement Inhibitor (SCIN) Protein Family.,Garcia BL, Summers BJ, Lin Z, Ramyar KX, Ricklin D, Kamath DV, Fu ZQ, Lambris JD, Geisbrecht BV J Biol Chem. 2012 Jan 2;287(1):628-40. Epub 2011 Nov 15. PMID:22086928<ref>PMID:22086928</ref>
-	~~[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role~~ in the ~~activation~~ of the ~~complement system~~. ~~Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently~~, ~~via its reactive thioester~~, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, ~~C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle~~, ~~increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes~~.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Acylation stimulating protein (~~ASP~~): ~~adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance~~. ~~Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways~~. ~~Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>~~PMID:~~8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref>~~ <ref>PMID:~~19615750~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3t4a]] is~~ a ~~8 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens] and [http://en~~.~~wikipedia.org~~/~~wiki/Staphylococcus_aureus_subsp._aureus_mu50 Staphylococcus aureus subsp. aureus mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:022086928</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Complement C3\|Complement C3]]
		+	*[[Fibrinogen binding protein\|Fibrinogen binding protein]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Staphylococcus aureus subsp. aureus mu50]]		[[Category: Staphylococcus aureus subsp. aureus mu50]]
-	[[Category: Garcia, B L.]]	+	[[Category: Garcia, B L]]
-	[[Category: Geisbrecht, B V.]]	+	[[Category: Geisbrecht, B V]]
-	[[Category: Summers, B J.]]	+	[[Category: Summers, B J]]
	[[Category: Age-related macular degeneration]]		[[Category: Age-related macular degeneration]]
	[[Category: Cleavage on pair of basic residue]]		[[Category: Cleavage on pair of basic residue]]

OCA at 06:30, 20 June 2013

OCA — Thu, 20 Jun 2013 06:30:42 GMT

←Older revision		Revision as of 06:30, 20 June 2013
Line 4:		Line 4:

	==Disease==		==Disease==
-	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[http://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref><ref>PMID:9596584</ref><ref>PMID:11387479</ref><ref>PMID:15713468</ref><ref>PMID:7961791</ref>[:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[http://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref><ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[http://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref><ref>PMID:18796626</ref><ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>	+	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[http://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref> <ref>PMID:9596584</ref> <ref>PMID:11387479</ref> <ref>PMID:15713468</ref> <ref>PMID:7961791</ref> [:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[http://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref> <ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[http://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref> <ref>PMID:18796626</ref> <ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>

	==Function==		==Function==
-	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref><ref>PMID:2909530</ref><ref>PMID:9059512</ref><ref>PMID:9555951</ref><ref>PMID:10432298</ref><ref>PMID:15833747</ref><ref>PMID:16333141</ref><ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref><ref>PMID:2909530</ref><ref>PMID:9059512</ref><ref>PMID:9555951</ref><ref>PMID:10432298</ref><ref>PMID:15833747</ref><ref>PMID:16333141</ref><ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref><ref>PMID:2909530</ref><ref>PMID:9059512</ref><ref>PMID:9555951</ref><ref>PMID:10432298</ref><ref>PMID:15833747</ref><ref>PMID:16333141</ref><ref>PMID:19615750</ref>	+	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref> <ref>PMID:2909530</ref> <ref>PMID:9059512</ref> <ref>PMID:9555951</ref> <ref>PMID:10432298</ref> <ref>PMID:15833747</ref> <ref>PMID:16333141</ref> <ref>PMID:19615750</ref>

	==About this Structure==		==About this Structure==
-	[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp.~~_aureus~~ Staphylococcus aureus subsp. aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].	+	[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_mu50 Staphylococcus aureus subsp. aureus mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].
-		+
-	~~==See Also==~~	+
-	*[[Fibrinogen binding protein\|Fibrinogen binding protein]]	+

	==Reference==		==Reference==
	<ref group="xtra">PMID:022086928</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:022086928</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Staphylococcus aureus subsp. aureus]]	+	[[Category: Staphylococcus aureus subsp. aureus mu50]]
	[[Category: Garcia, B L.]]		[[Category: Garcia, B L.]]
	[[Category: Geisbrecht, B V.]]		[[Category: Geisbrecht, B V.]]

OCA at 03:55, 25 March 2013

OCA — Mon, 25 Mar 2013 03:55:42 GMT

←Older revision		Revision as of 03:55, 25 March 2013
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-	[[Image:3t4a.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3t4a", 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),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3t4a\| PDB=3t4a \| SCENE= }}		{{STRUCTURE_3t4a\| PDB=3t4a \| SCENE= }}
-
	===Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution===		===Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution===
		+	{{ABSTRACT_PUBMED_22086928}}

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:[http://omim.org/entry/613779 613779]]. A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.<ref>PMID:19913840</ref><ref>PMID:9596584</ref><ref>PMID:11387479</ref><ref>PMID:15713468</ref><ref>PMID:7961791</ref>[:] Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:[http://omim.org/entry/611378 611378]]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:19913840</ref><ref>PMID:17634448</ref> Defects in C3 are a cause of susceptibility to hemolytic uremic syndrome atypical type 5 (AHUS5) [MIM:[http://omim.org/entry/612925 612925]]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19913840</ref><ref>PMID:18796626</ref><ref>PMID:20513133</ref> Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage.<ref>PMID:19913840</ref>

-	~~<!--~~	+	==Function==
-	~~The line below this paragraph~~, ~~{{ABSTRACT_PUBMED_22086928}}~~, ~~adds the Publication Abstract~~ to ~~the page~~	+	[[http://www.uniprot.org/uniprot/CO3_HUMAN CO3_HUMAN]] C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.<ref>PMID:8376604</ref><ref>PMID:2909530</ref><ref>PMID:9059512</ref><ref>PMID:9555951</ref><ref>PMID:10432298</ref><ref>PMID:15833747</ref><ref>PMID:16333141</ref><ref>PMID:19615750</ref> Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.<ref>PMID:8376604</ref><ref>PMID:2909530</ref><ref>PMID:9059512</ref><ref>PMID:9555951</ref><ref>PMID:10432298</ref><ref>PMID:15833747</ref><ref>PMID:16333141</ref><ref>PMID:19615750</ref> Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for GPR77. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of GPR77.<ref>PMID:8376604</ref><ref>PMID:2909530</ref><ref>PMID:9059512</ref><ref>PMID:9555951</ref><ref>PMID:10432298</ref><ref>PMID:15833747</ref><ref>PMID:16333141</ref><ref>PMID:19615750</ref>
-	~~(as it appears on PubMed at http~~://~~www~~.~~pubmed~~.~~gov~~), ~~where 22086928 is~~ the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_22086928}}~~	+

	==About this Structure==		==About this Structure==
	[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus Staphylococcus aureus subsp. aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].		[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus Staphylococcus aureus subsp. aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].
		+
		+	==See Also==
		+	*[[Fibrinogen binding protein\|Fibrinogen binding protein]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022086928</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022086928</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Staphylococcus aureus subsp. aureus]]		[[Category: Staphylococcus aureus subsp. aureus]]

OCA at 09:30, 18 January 2012

OCA — Wed, 18 Jan 2012 09:30:23 GMT

←Older revision		Revision as of 09:30, 18 January 2012
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-	[[Image:3t4a.~~jpg~~\|left\|200px]]	+	[[Image:3t4a.png\|left\|200px]]

	<!--		<!--
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	===Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution===		===Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22086928}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22086928 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22086928}}

	==About this Structure==		==About this Structure==
	[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus Staphylococcus aureus subsp. aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].		[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus Staphylococcus aureus subsp. aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022086928</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Staphylococcus aureus subsp. aureus]]		[[Category: Staphylococcus aureus subsp. aureus]]

OCA at 19:16, 23 November 2011

OCA — Wed, 23 Nov 2011 19:16:26 GMT

←Older revision		Revision as of 19:16, 23 November 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3t4a.jpg\|left\|200px]]

-	The ~~entry 3t4a~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3t4a", 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),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3t4a\| PDB=3t4a \| SCENE= }}

-	~~Authors: Garcia,~~ B.~~L., Geisbrecht, B.V., Summers, B.J.~~	+	===Structure of a truncated form of Staphylococcal Complement Inhibitor B bound to human C3c at 3.4 Angstrom resolution===

-	~~Description~~: ~~Evidence for diversity in both the C3b contact residues~~ and ~~tertiary structures~~ of ~~the staphylococcal complement inhibitor (SCIN) protein family~~	+
		+	==About this Structure==
		+	[[3t4a]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus Staphylococcus aureus subsp. aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T4A OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Staphylococcus aureus subsp. aureus]]
		+	[[Category: Garcia, B L.]]
		+	[[Category: Geisbrecht, B V.]]
		+	[[Category: Summers, B J.]]
		+	[[Category: Age-related macular degeneration]]
		+	[[Category: Cleavage on pair of basic residue]]
		+	[[Category: Complement alternate pathway]]
		+	[[Category: Complement pathway]]
		+	[[Category: Disease mutation]]
		+	[[Category: Disulfide bond]]
		+	[[Category: Glycoprotein]]
		+	[[Category: Hemolytic uremic syndrome]]
		+	[[Category: Immune system]]
		+	[[Category: Immunity]]
		+	[[Category: Inflammatory response]]
		+	[[Category: Innate immunity]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Secreted]]
		+	[[Category: Thioester bond]]

OCA at 07:08, 24 August 2011

OCA — Wed, 24 Aug 2011 07:08:38 GMT

←Older revision		Revision as of 07:08, 24 August 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3t4a is ON HOLD	+	The entry 3t4a is ON HOLD until Paper Publication

	Authors: Garcia, B.L., Geisbrecht, B.V., Summers, B.J.		Authors: Garcia, B.L., Geisbrecht, B.V., Summers, B.J.

	Description: Evidence for diversity in both the C3b contact residues and tertiary structures of the staphylococcal complement inhibitor (SCIN) protein family		Description: Evidence for diversity in both the C3b contact residues and tertiary structures of the staphylococcal complement inhibitor (SCIN) protein family