3t3p - Revision history

OCA at 16:41, 6 July 2022

OCA — Wed, 06 Jul 2022 16:41:45 GMT

←Older revision		Revision as of 16:41, 6 July 2022
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	==A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS==		==A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS==
-	<StructureSection load='3t3p' size='340' side='right' caption='[[3t3p]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='3t3p' size='340' side='right'caption='[[3t3p]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t3p]] is a 8 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human] and [~~http~~://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3T3P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t3p]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T3P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL~~</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN~~</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nid\|3nid]], [[3nif\|3nif]], [[3nig\|3nig]], [[2vdr\|2vdr]], [[3t3m\|3t3m]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nid\|3nid]], [[3nif\|3nif]], [[3nig\|3nig]], [[2vdr\|2vdr]], [[3t3m\|3t3m]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGA2B, GP2B, ITGAB ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGA2B, GP2B, ITGAB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3t3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t3p OCA], [~~http~~://pdbe.org/3t3p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3t3p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3t3p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3t3p 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=3t3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t3p OCA], [https://pdbe.org/3t3p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t3p RCSB], [https://www.ebi.ac.uk/pdbsum/3t3p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t3p ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Defects in ITGA2B are a cause of Glanzmann thrombasthenia (GT) [MIM:[~~http~~://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:8282784</ref> <ref>PMID:7508443</ref> <ref>PMID:7706461</ref> <ref>PMID:8704171</ref> <ref>PMID:9215749</ref> <ref>PMID:9473221</ref> <ref>PMID:9763559</ref> <ref>PMID:9722314</ref> <ref>PMID:9734640</ref> <ref>PMID:9920835</ref> <ref>PMID:10607701</ref> <ref>PMID:11798398</ref> <ref>PMID:12181054</ref> <ref>PMID:12083483</ref> <ref>PMID:12424194</ref> <ref>PMID:12506038</ref> <ref>PMID:15099289</ref> <ref>PMID:15219201</ref> <ref>PMID:17018384</ref> [[~~http~~://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[~~http~~://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:2392682</ref> <ref>PMID:1371279</ref> <ref>PMID:1602006</ref> <ref>PMID:1438206</ref> <ref>PMID:8781422</ref> <ref>PMID:9376589</ref> <ref>PMID:9215749</ref> <ref>PMID:9790984</ref> <ref>PMID:9684783</ref> <ref>PMID:10233432</ref> <ref>PMID:11588040</ref> <ref>PMID:11897046</ref> <ref>PMID:12083483</ref> <ref>PMID:12353082</ref> <ref>PMID:15583747</ref> <ref>PMID:15634267</ref> <ref>PMID:15748237</ref>	+	[[https://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Defects in ITGA2B are a cause of Glanzmann thrombasthenia (GT) [MIM:[https://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:8282784</ref> <ref>PMID:7508443</ref> <ref>PMID:7706461</ref> <ref>PMID:8704171</ref> <ref>PMID:9215749</ref> <ref>PMID:9473221</ref> <ref>PMID:9763559</ref> <ref>PMID:9722314</ref> <ref>PMID:9734640</ref> <ref>PMID:9920835</ref> <ref>PMID:10607701</ref> <ref>PMID:11798398</ref> <ref>PMID:12181054</ref> <ref>PMID:12083483</ref> <ref>PMID:12424194</ref> <ref>PMID:12506038</ref> <ref>PMID:15099289</ref> <ref>PMID:15219201</ref> <ref>PMID:17018384</ref> [[https://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[https://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:2392682</ref> <ref>PMID:1371279</ref> <ref>PMID:1602006</ref> <ref>PMID:1438206</ref> <ref>PMID:8781422</ref> <ref>PMID:9376589</ref> <ref>PMID:9215749</ref> <ref>PMID:9790984</ref> <ref>PMID:9684783</ref> <ref>PMID:10233432</ref> <ref>PMID:11588040</ref> <ref>PMID:11897046</ref> <ref>PMID:12083483</ref> <ref>PMID:12353082</ref> <ref>PMID:15583747</ref> <ref>PMID:15634267</ref> <ref>PMID:15748237</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. [[~~http~~://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.	+	[[https://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. [[https://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 24:

	==See Also==		==See Also==
-	*[[3D structures ~~of monoclonal antibody~~\|3D structures ~~of monoclonal antibody~~]]	+	*[[Integrin 3D structures\|Integrin 3D structures]]
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Springer, T A]]		[[Category: Springer, T A]]

OCA at 09:42, 25 October 2017

OCA — Wed, 25 Oct 2017 09:42:31 GMT

←Older revision		Revision as of 09:42, 25 October 2017
Line 3:		Line 3:
	<StructureSection load='3t3p' size='340' side='right' caption='[[3t3p]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3t3p' size='340' side='right' caption='[[3t3p]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T3P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T3P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4~~</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN~~</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nid\|3nid]], [[3nif\|3nif]], [[3nig\|3nig]], [[2vdr\|2vdr]], [[3t3m\|3t3m]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nid\|3nid]], [[3nif\|3nif]], [[3nig\|3nig]], [[2vdr\|2vdr]], [[3t3m\|3t3m]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGA2B, GP2B, ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGA2B, GP2B, ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
Line 24:		Line 24:

	==See Also==		==See Also==
-	*[[Integrin\|Integrin]]
	*[[3D structures of monoclonal antibody\|3D structures of monoclonal antibody]]		*[[3D structures of monoclonal antibody\|3D structures of monoclonal antibody]]
	== References ==		== References ==
Line 31:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
	[[Category: Springer, T A]]		[[Category: Springer, T A]]
	[[Category: Zhu, J]]		[[Category: Zhu, J]]

OCA at 11:26, 5 August 2016

OCA — Fri, 05 Aug 2016 11:26:21 GMT

←Older revision		Revision as of 11:26, 5 August 2016
Line 1:		Line 1:
		+
	==A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS==		==A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS==
	<StructureSection load='3t3p' size='340' side='right' caption='[[3t3p]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3t3p' size='340' side='right' caption='[[3t3p]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~] and [http://en.wikipedia.org/wiki/~~Mus_musculus Mus musculus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T3P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T3P FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nid\|3nid]], [[3nif\|3nif]], [[3nig\|3nig]], [[2vdr\|2vdr]], [[3t3m\|3t3m]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nid\|3nid]], [[3nif\|3nif]], [[3nig\|3nig]], [[2vdr\|2vdr]], [[3t3m\|3t3m]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGA2B, GP2B, ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), ITGB3, GP3A ([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">ITGA2B, GP2B, ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB3, GP3A ([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=3t3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t3p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t3p RCSB], [http://www.ebi.ac.uk/pdbsum/3t3p 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=3t3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t3p OCA], [http://pdbe.org/3t3p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t3p RCSB], [http://www.ebi.ac.uk/pdbsum/3t3p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t3p ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 3t3p" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Integrin\|Integrin]]		*[[Integrin\|Integrin]]
-	*[[~~Monoclonal Antibody~~\|~~Monoclonal Antibody~~]]	+	*[[3D structures of monoclonal antibody\|3D structures of monoclonal antibody]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
-	[[Category: ~~Mus musculus~~]]	+	[[Category: Lk3 transgenic mice]]
	[[Category: Springer, T A]]		[[Category: Springer, T A]]
	[[Category: Zhu, J]]		[[Category: Zhu, J]]

OCA at 07:20, 21 December 2014

OCA — Sun, 21 Dec 2014 07:20:55 GMT

←Older revision		Revision as of 07:20, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3t3p\| PDB=3t3p \| SCENE= }}~~	+	==A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS==
-	===A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS===	+	<StructureSection load='3t3p' size='340' side='right' caption='[[3t3p]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22422993}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T3P FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3nid\|3nid]], [[3nif\|3nif]], [[3nig\|3nig]], [[2vdr\|2vdr]], [[3t3m\|3t3m]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITGA2B, GP2B, ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ITGB3, GP3A ([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=3t3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t3p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3t3p RCSB], [http://www.ebi.ac.uk/pdbsum/3t3p PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Defects in ITGA2B are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:8282784</ref> <ref>PMID:7508443</ref> <ref>PMID:7706461</ref> <ref>PMID:8704171</ref> <ref>PMID:9215749</ref> <ref>PMID:9473221</ref> <ref>PMID:9763559</ref> <ref>PMID:9722314</ref> <ref>PMID:9734640</ref> <ref>PMID:9920835</ref> <ref>PMID:10607701</ref> <ref>PMID:11798398</ref> <ref>PMID:12181054</ref> <ref>PMID:12083483</ref> <ref>PMID:12424194</ref> <ref>PMID:12506038</ref> <ref>PMID:15099289</ref> <ref>PMID:15219201</ref> <ref>PMID:17018384</ref> [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:2392682</ref> <ref>PMID:1371279</ref> <ref>PMID:1602006</ref> <ref>PMID:1438206</ref> <ref>PMID:8781422</ref> <ref>PMID:9376589</ref> <ref>PMID:9215749</ref> <ref>PMID:9790984</ref> <ref>PMID:9684783</ref> <ref>PMID:10233432</ref> <ref>PMID:11588040</ref> <ref>PMID:11897046</ref> <ref>PMID:12083483</ref> <ref>PMID:12353082</ref> <ref>PMID:15583747</ref> <ref>PMID:15634267</ref> <ref>PMID:15748237</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	An integrin found on platelets, alpha(IIb)beta(3) mediates platelet aggregation, and alpha(IIb)beta(3) antagonists are effective antithrombotic agents in the clinic. Ligands bind to integrins in part by coordinating a magnesium ion (Mg(2+)) located in the beta subunit metal ion-dependent adhesion site (MIDAS). Drugs patterned on the integrin ligand sequence Arg-Gly-Asp have a basic moiety that binds the alpha(IIb) subunit and a carboxyl group that coordinates the MIDAS Mg(2+) in the beta(3) subunits. They induce conformational changes in the beta(3) subunit that may have negative consequences such as exposing previously hidden epitopes and inducing the active conformation of the receptor. We recently reported an inhibitor of alpha(IIb)beta(3) (RUC-1) that binds exclusively to the alpha(IIb) subunit; here, we report the structure-based design and synthesis of RUC-2, a RUC-1 derivative with a ~100-fold higher affinity. RUC-2 does not induce major conformational changes in beta(3) as judged by monoclonal antibody binding, light scattering, gel chromatography, electron microscopy, and a receptor priming assay. X-ray crystallography of the RUC-2-alpha(IIb)beta(3) headpiece complex in 1 mM calcium ion (Ca(2+))/5 mM Mg(2+) at 2.6 A revealed that RUC-2 binds to alpha(IIb) the way RUC-1 does, but in addition, it binds to the beta(3) MIDAS residue glutamic acid 220, thus displacing Mg(2+) from the MIDAS. When the Mg(2+) concentration was increased to 20 mM, however, Mg(2+) was identified in the MIDAS and RUC-2 was absent. RUC-2's ability to inhibit ligand binding and platelet aggregation was diminished by increasing the Mg(2+) concentration. Thus, RUC-2 inhibits ligand binding by a mechanism different from that of all other alpha(IIb)beta(3) antagonists and may offer advantages as a therapeutic agent.

-	~~==Disease==~~	+	Structure-Guided Design of a High-Affinity Platelet Integrin alphaIIbbeta3 Receptor Antagonist That Disrupts Mg2+ Binding to the MIDAS.,Zhu J, Choi WS, McCoy JG, Negri A, Zhu J, Naini S, Li J, Shen M, Huang W, Bougie D, Rasmussen M, Aster R, Thomas CJ, Filizola M, Springer TA, Coller BS Sci Transl Med. 2012 Mar 14;4(125):125ra32. PMID:22422993<ref>PMID:22422993</ref>
-	~~[[http://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Defects in ITGA2B are~~ a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to~~-moderate severity and~~ the ~~inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II~~. ~~In type I~~, ~~platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II~~, ~~the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls)~~, ~~have detectable amounts of fibrinogen~~, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:8282784</ref><ref>PMID:7508443</ref><ref>PMID:7706461</ref><ref>PMID:8704171</ref><ref>PMID:9215749</ref><ref>PMID:9473221</ref><ref>PMID:9763559</ref><ref>PMID:9722314</ref><ref>PMID:9734640</ref><ref>PMID:9920835</ref><ref>PMID:10607701</ref><ref>PMID:11798398</ref><ref>PMID:12181054</ref><ref>PMID:12083483</ref><ref>PMID:12424194</ref><ref>PMID:12506038</ref><ref>PMID:15099289</ref><ref>PMID:15219201</ref><ref>PMID:17018384</ref> [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, ~~platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II~~, ~~the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls)~~, ~~have detectable amounts of fibrinogen~~, ~~and have low or moderate clot retraction capability~~. ~~The platelets of GT 'variants' have normal or near normal~~ (~~60-100%~~) ~~expression of dysfunctional receptors~~.~~<ref>~~PMID:2392682</ref><ref>PMID:1371279</ref><ref>PMID:1602006</ref><ref>PMID:1438206</ref><ref>PMID:8781422</ref><ref>PMID:9376589</ref><ref>PMID:9215749</ref><ref>PMID:9790984</ref><ref>PMID:9684783</ref><ref>PMID:10233432</ref><ref>PMID:11588040</ref><ref>PMID:11897046</ref><ref>PMID:12083483</ref><ref>PMID:12353082</ref><ref>PMID:15583747</ref><ref>PMID:15634267</ref><ref>PMID:~~15748237~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Integrin alpha-IIb/beta-3 is a receptor for fibronectin~~, ~~fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in~~ a ~~wide array~~ of ~~ligands. It recognizes~~ the ~~sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain~~. ~~Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen~~. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.	+	</div>
-		+
-	~~==About this Structure==~~	+
-	~~[[3t3p]] is a 8 chain structure with sequence from [http:~~//en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA].	+

	==See Also==		==See Also==
	*[[Integrin\|Integrin]]		*[[Integrin\|Integrin]]
	*[[Monoclonal Antibody\|Monoclonal Antibody]]		*[[Monoclonal Antibody\|Monoclonal Antibody]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:022422993</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
-	[[Category: Springer, T A.]]	+	[[Category: Springer, T A]]
-	[[Category: Zhu, J.]]	+	[[Category: Zhu, J]]
	[[Category: Blood clotting]]		[[Category: Blood clotting]]
	[[Category: Cell adhesion]]		[[Category: Cell adhesion]]

OCA at 21:17, 24 March 2013

OCA — Sun, 24 Mar 2013 21:17:36 GMT

←Older revision		Revision as of 21:17, 24 March 2013
Line 1:		Line 1:
-	[[Image:3t3p.png\|left\|200px]]
-
	{{STRUCTURE_3t3p\| PDB=3t3p \| SCENE= }}		{{STRUCTURE_3t3p\| PDB=3t3p \| SCENE= }}
-
	===A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS===		===A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS===
		+	{{ABSTRACT_PUBMED_22422993}}

-	~~{{ABSTRACT_PUBMED_22422993}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Defects in ITGA2B are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:8282784</ref><ref>PMID:7508443</ref><ref>PMID:7706461</ref><ref>PMID:8704171</ref><ref>PMID:9215749</ref><ref>PMID:9473221</ref><ref>PMID:9763559</ref><ref>PMID:9722314</ref><ref>PMID:9734640</ref><ref>PMID:9920835</ref><ref>PMID:10607701</ref><ref>PMID:11798398</ref><ref>PMID:12181054</ref><ref>PMID:12083483</ref><ref>PMID:12424194</ref><ref>PMID:12506038</ref><ref>PMID:15099289</ref><ref>PMID:15219201</ref><ref>PMID:17018384</ref> [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://omim.org/entry/273800 273800]]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:2392682</ref><ref>PMID:1371279</ref><ref>PMID:1602006</ref><ref>PMID:1438206</ref><ref>PMID:8781422</ref><ref>PMID:9376589</ref><ref>PMID:9215749</ref><ref>PMID:9790984</ref><ref>PMID:9684783</ref><ref>PMID:10233432</ref><ref>PMID:11588040</ref><ref>PMID:11897046</ref><ref>PMID:12083483</ref><ref>PMID:12353082</ref><ref>PMID:15583747</ref><ref>PMID:15634267</ref><ref>PMID:15748237</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface. [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

	==About this Structure==		==About this Structure==
Line 15:		Line 17:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022422993</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022422993</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mus musculus]]		[[Category: Mus musculus]]

OCA at 19:57, 20 October 2012

OCA — Sat, 20 Oct 2012 19:57:51 GMT

←Older revision		Revision as of 19:57, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3t3p]] is a 8 chain structure ~~of [[Monoclonal Antibody]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA].	+	[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA].

	==See Also==		==See Also==
		+	*[[Integrin\|Integrin]]
	*[[Monoclonal Antibody\|Monoclonal Antibody]]		*[[Monoclonal Antibody\|Monoclonal Antibody]]

OCA at 09:00, 27 July 2012

OCA — Fri, 27 Jul 2012 09:00:53 GMT

←Older revision		Revision as of 09:00, 27 July 2012
Line 1:		Line 1:
-	[[Image:3t3p.~~jpg~~\|left\|200px]]	+	[[Image:3t3p.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3t3p", 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_3t3p\| PDB=3t3p \| SCENE= }}		{{STRUCTURE_3t3p\| PDB=3t3p \| SCENE= }}

	===A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS===		===A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22422993}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22422993 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_22422993}}		{{ABSTRACT_PUBMED_22422993}}

	==About this Structure==		==About this Structure==
-	[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA].	+	[[3t3p]] is a 8 chain structure of [[Monoclonal Antibody]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA].
		+
		+	==See Also==
		+	*[[Monoclonal Antibody\|Monoclonal Antibody]]

	==Reference==		==Reference==

OCA at 07:41, 28 March 2012

OCA — Wed, 28 Mar 2012 07:41:48 GMT

←Older revision		Revision as of 07:41, 28 March 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3t3p.jpg\|left\|200px]]

-	The ~~entry 3t3p~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3t3p", 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_3t3p\| PDB=3t3p \| SCENE= }}

-	~~Authors: Zhu, J., Zhu, J., Springer, T.~~A.	+	===A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS===

-	~~Description~~: A ~~Novel High Affinity~~ Integrin ~~alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22422993}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22422993 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22422993}}
		+
		+	==About this Structure==
		+	[[3t3p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T3P OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022422993</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Mus musculus]]
		+	[[Category: Springer, T A.]]
		+	[[Category: Zhu, J.]]
		+	[[Category: Blood clotting]]
		+	[[Category: Cell adhesion]]
		+	[[Category: Fibrinogen]]
		+	[[Category: Integrin]]
		+	[[Category: Platelet]]

OCA at 06:01, 14 September 2011

OCA — Wed, 14 Sep 2011 06:01:39 GMT

←Older revision		Revision as of 06:01, 14 September 2011
Line 3:		Line 3:
	The entry 3t3p is ON HOLD		The entry 3t3p is ON HOLD

-	Authors: Zhu, J, Zhu, J, Springer, T.A.	+	Authors: Zhu, J., Zhu, J., Springer, T.A.

	Description: A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS		Description: A Novel High Affinity Integrin alphaIIbbeta3 Receptor Antagonist That Unexpectedly Displaces Mg2+ from the beta3 MIDAS

OCA: Protected "3t3p" [edit=sysop:move=sysop]

OCA — Wed, 03 Aug 2011 08:25:45 GMT

Protected "3t3p" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:25, 3 August 2011