7tct - Revision history

OCA at 09:44, 25 October 2023

2023-10-25T09:44:56Z

←Older revision		Revision as of 09:44, 25 October 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7tct]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7TCT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TCT FirstGlance]. <br>		<table><tr><td colspan='2'>[[7tct]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7TCT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TCT FirstGlance]. <br>
-	</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=I1F:{5-[N-(4-carbamimidoylbenzoyl)-4-nitro-L-phenylalanyl]-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl}acetic+acid'>I1F</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='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.501Å</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=I1F:{5-[N-(4-carbamimidoylbenzoyl)-4-nitro-L-phenylalanyl]-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl}acetic+acid'>I1F</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7tct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tct OCA], [https://pdbe.org/7tct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tct RCSB], [https://www.ebi.ac.uk/pdbsum/7tct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tct 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=7tct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tct OCA], [https://pdbe.org/7tct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tct RCSB], [https://www.ebi.ac.uk/pdbsum/7tct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tct ProSAT]</span></td></tr>
	</table>		</table>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 7tct" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7tct" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Integrin 3D structures\|Integrin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:43, 8 March 2023

2023-03-08T07:43:19Z

←Older revision		Revision as of 07:43, 8 March 2023
Line 1:		Line 1:

-	====	+	==Integrin alaphIIBbeta3 complex with UR2922==
-	<StructureSection load='7tct' size='340' side='right'caption='[[7tct]]' scene=''>	+	<StructureSection load='7tct' size='340' side='right'caption='[[7tct]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7tct]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7TCT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TCT FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7tct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tct OCA], [https://pdbe.org/7tct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tct RCSB], [https://www.ebi.ac.uk/pdbsum/7tct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tct ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=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=I1F:{5-[N-(4-carbamimidoylbenzoyl)-4-nitro-L-phenylalanyl]-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl}acetic+acid'>I1F</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7tct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tct OCA], [https://pdbe.org/7tct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tct RCSB], [https://www.ebi.ac.uk/pdbsum/7tct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tct ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[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>
		+	== Function ==
		+	[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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Integrins are validated drug targets with six approved therapeutics. However, small-molecule inhibitors to three integrins failed in late-stage clinical trials for chronic indications. Such unfavorable outcomes may in part be caused by partial agonism, i.e., the stabilization of the high-affinity, extended-open integrin conformation. Here, we show that the failed, small-molecule inhibitors of integrins alphaIIbbeta3 and alpha4beta1 stabilize the high-affinity conformation. Furthermore, we discovered a simple chemical feature present in multiple alphaIIbbeta3 antagonists that stabilizes integrins in their bent-closed conformation. Closing inhibitors contain a polar nitrogen atom that stabilizes, via hydrogen bonds, a water molecule that intervenes between a serine residue and the metal in the metal-ion-dependent adhesion site (MIDAS). Expulsion of this water is a requisite for transition to the open conformation. This change in metal coordination is general to integrins, suggesting broad applicability of the drug-design principle to the integrin family, as validated with a distantly related integrin, alpha4beta1.
		+
		+	A general chemical principle for creating closure-stabilizing integrin inhibitors.,Lin FY, Li J, Xie Y, Zhu J, Huong Nguyen TT, Zhang Y, Zhu J, Springer TA Cell. 2022 Sep 15;185(19):3533-3550.e27. doi: 10.1016/j.cell.2022.08.008. PMID:36113427<ref>PMID:36113427</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7tct" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z-~~disk~~]]	+	[[Category: Mus musculus]]
		+	[[Category: Lin F-Y]]
		+	[[Category: Springer TA]]
		+	[[Category: Zhu J]]

OCA at 06:19, 18 August 2022

2022-08-18T06:19:46Z

←Older revision		Revision as of 06:19, 18 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7tct ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7tct' size='340' side='right'caption='[[7tct]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7tct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tct OCA], [https://pdbe.org/7tct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tct RCSB], [https://www.ebi.ac.uk/pdbsum/7tct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tct ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 10:21, 27 April 2022

2022-04-27T10:21:35Z

←Older revision		Revision as of 10:21, 27 April 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7tct is ON HOLD	+	The entry 7tct is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7tct" [edit=sysop:move=sysop]

2022-01-05T09:21:19Z

Protected "7tct" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:21, 5 January 2022

OCA: New page: '''Unreleased structure''' The entry 7tct is ON HOLD Authors: Description: Category: Unreleased Structures

2022-01-05T09:21:18Z

New page: '''Unreleased structure''' The entry 7tct is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7tct is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]