3nif

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{{Seed}}
 
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[[Image:3nif.jpg|left|200px]]
 
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==The Closed Headpiece of Integrin IIb 3 and its Complex with an IIb 3 -Specific Antagonist That Does Not Induce Opening==
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The line below this paragraph, containing "STRUCTURE_3nif", creates the "Structure Box" on the page.
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<StructureSection load='3nif' size='340' side='right'caption='[[3nif]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3nif]] 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=3NIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NIF FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=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=NIF:2-ETHYL-7-PIPERAZIN-1-YL-5H-[1,3,4]THIADIAZOLO[3,2-A]PYRIMIDIN-5-ONE'>NIF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_3nif| PDB=3nif | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nif OCA], [https://pdbe.org/3nif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nif RCSB], [https://www.ebi.ac.uk/pdbsum/3nif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nif ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The platelet integrin alpha(IIb)beta(3) is essential for hemostasis and thrombosis through its binding of adhesive plasma proteins. We have determined crystal structures of the alpha(IIb)beta(3) headpiece in the absence of ligand and after soaking in RUC-1, a novel small molecule antagonist. In the absence of ligand, the alpha(IIb)beta(3) headpiece is in a closed conformation, distinct from the open conformation visualized in presence of Arg-Gly-Asp (RGD) antagonists. In contrast to RGD antagonists, RUC-1 binds only to the alpha(IIb) subunit. Molecular dynamics revealed nearly identical binding. Two species-specific residues, alpha(IIb) Y190 and alpha(IIb) D232, in the RUC-1 binding site were confirmed as important by mutagenesis. In sharp contrast to RGD-based antagonists, RUC-1 did not induce alpha(IIb)beta(3) to adopt an open conformation, as determined by gel filtration and dynamic light scattering. These studies provide insights into the factors that regulate integrin headpiece opening, and demonstrate the molecular basis for a novel mechanism of integrin antagonism.
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===The Closed Headpiece of Integrin IIb 3 and its Complex with an IIb 3 -Specific Antagonist That Does Not Induce Opening===
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Closed headpiece of integrin alphaIIbbeta3 and its complex with an alphaIIbbeta3-specific antagonist that does not induce opening.,Zhu J, Zhu J, Negri A, Provasi D, Filizola M, Coller BS, Springer TA Blood. 2010 Dec 2;116(23):5050-9. Epub 2010 Aug 2. PMID:20679525<ref>PMID:20679525</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3nif" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20679525}}, adds the Publication Abstract to the page
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*[[Integrin 3D structures|Integrin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20679525 is the PubMed ID number.
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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== References ==
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{{ABSTRACT_PUBMED_20679525}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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3NIF is a 8 chains structure with sequences 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=3NIF OCA].
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==Reference==
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<ref group="xtra">PMID:20679525</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Springer, T A.]]
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[[Category: Springer TA]]
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[[Category: Zhu, J H.]]
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[[Category: Zhu JH]]
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[[Category: Zhu, J Q.]]
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[[Category: Zhu JQ]]
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[[Category: Alphaiib]]
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[[Category: Beta3]]
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[[Category: Cell adhesion-blood clotting complex]]
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[[Category: Headpiece]]
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[[Category: Integrin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 22 09:54:15 2010''
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Current revision

The Closed Headpiece of Integrin IIb 3 and its Complex with an IIb 3 -Specific Antagonist That Does Not Induce Opening

PDB ID 3nif

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