3p72: Difference between revisions
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==structure of platelet Glycoprotein 1b alpha with a bound peptide inhibitor== | |||
<StructureSection load='3p72' size='340' side='right'caption='[[3p72]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3p72]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P72 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=3p72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p72 OCA], [https://pdbe.org/3p72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p72 RCSB], [https://www.ebi.ac.uk/pdbsum/3p72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p72 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[https://omim.org/entry/258660 258660]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[https://omim.org/entry/231200 231200]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[https://omim.org/entry/153670 153670]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[https://omim.org/entry/177820 177820]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Platelet glycoprotein Ibalpha (GpIbalpha) interactions with von Willebrand factor (VWF) are a critical early event in platelet adhesion, which contributes to hemostasis and thrombosis. Here we report the structure of a complex between GpIbalpha and a potent peptide inhibitor. The cyclic peptide (CTERMALHNLC) was isolated from a cysteine-constrained phage display library, and in the complex this forms one and a half turns of an amphipathic alpha-helix, the curvature of which facilitates contacts with the curved concave face of the GpIbalpha leucine-rich repeats. The peptide has only limited overlap with the VWF binding site. It effectively inhibits by stabilizing an alternative alpha-helical conformation of a regulatory loop that forms an extended beta-hairpin upon VWF binding. The structure defines a previously unrecognized binding site within GpIbalpha and represents a clear strategy for developing antiplatelet agents targeting the GpIbalpha-VWF interaction allosterically. | |||
Glycoprotein Ibalpha inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism.,McEwan PA, Andrews RK, Emsley J Blood. 2009 Nov 26;114(23):4883-5. doi: 10.1182/blood-2009-05-224170. Epub 2009, Sep 2. PMID:19726719<ref>PMID:19726719</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3p72" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Platelet | *[[Platelet glycoprotein|Platelet glycoprotein]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Andrews RK]] | ||
[[Category: | [[Category: Emsley J]] | ||
[[Category: | [[Category: McEwan PA]] | ||