3hxo
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:3hxo.png|left|200px]] | ||
| - | |||
| - | <!-- | ||
| - | The line below this paragraph, containing "STRUCTURE_3hxo", 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_3hxo| PDB=3hxo | SCENE= }} | {{STRUCTURE_3hxo| PDB=3hxo | SCENE= }} | ||
| - | |||
===Crystal Structure of Von Willebrand Factor (VWF) A1 Domain in Complex with DNA Aptamer ARC1172, an Inhibitor of VWF-Platelet Binding=== | ===Crystal Structure of Von Willebrand Factor (VWF) A1 Domain in Complex with DNA Aptamer ARC1172, an Inhibitor of VWF-Platelet Binding=== | ||
| + | {{ABSTRACT_PUBMED_19913482}} | ||
| + | ==Disease== | ||
| + | [[http://www.uniprot.org/uniprot/VWF_HUMAN VWF_HUMAN]] Defects in VWF are the cause of von Willebrand disease type 1 (VWD1) [MIM:[http://omim.org/entry/193400 193400]]. A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.<ref>PMID:10887119</ref><ref>PMID:11698279</ref> Defects in VWF are the cause of von Willebrand disease type 2 (VWD2) [MIM:[http://omim.org/entry/613554 613554]]. A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. Defects in VWF are the cause of von Willebrand disease type 3 (VWD3) [MIM:[http://omim.org/entry/277480 277480]]. A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses. | ||
| - | + | ==Function== | |
| - | + | [[http://www.uniprot.org/uniprot/VWF_HUMAN VWF_HUMAN]] Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma. | |
| - | + | ||
| - | -- | + | |
| - | + | ||
==About this Structure== | ==About this Structure== | ||
| Line 22: | Line 13: | ||
==Reference== | ==Reference== | ||
| - | <ref group="xtra">PMID:019913482</ref><ref group="xtra">PMID:018025536</ref><ref group="xtra">PMID:019422452</ref><references group="xtra"/> | + | <ref group="xtra">PMID:019913482</ref><ref group="xtra">PMID:018025536</ref><ref group="xtra">PMID:019422452</ref><references group="xtra"/><references/> |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Diener, J L.]] | [[Category: Diener, J L.]] | ||
Revision as of 05:18, 25 March 2013
Contents |
Crystal Structure of Von Willebrand Factor (VWF) A1 Domain in Complex with DNA Aptamer ARC1172, an Inhibitor of VWF-Platelet Binding
Template:ABSTRACT PUBMED 19913482
Disease
[VWF_HUMAN] Defects in VWF are the cause of von Willebrand disease type 1 (VWD1) [MIM:193400]. A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.[1][2] Defects in VWF are the cause of von Willebrand disease type 2 (VWD2) [MIM:613554]. A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. Defects in VWF are the cause of von Willebrand disease type 3 (VWD3) [MIM:277480]. A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses.
Function
[VWF_HUMAN] Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.
About this Structure
3hxo is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Huang RH, Fremont DH, Diener JL, Schaub RG, Sadler JE. A structural explanation for the antithrombotic activity of ARC1172, a DNA aptamer that binds von Willebrand factor domain A1. Structure. 2009 Nov 11;17(11):1476-84. PMID:19913482 doi:10.1016/j.str.2009.09.011
- Gilbert JC, DeFeo-Fraulini T, Hutabarat RM, Horvath CJ, Merlino PG, Marsh HN, Healy JM, Boufakhreddine S, Holohan TV, Schaub RG. First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Circulation. 2007 Dec 4;116(23):2678-86. Epub 2007 Nov 19. PMID:18025536 doi:10.1161/CIRCULATIONAHA.107.724864
- Diener JL, Daniel Lagasse HA, Duerschmied D, Merhi Y, Tanguay JF, Hutabarat R, Gilbert J, Wagner DD, Schaub R. Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779. J Thromb Haemost. 2009 Jul;7(7):1155-62. Epub 2009 Apr 24. PMID:19422452 doi:10.1111/j.1538-7836.2009.03459.x
- ↑ Allen S, Abuzenadah AM, Hinks J, Blagg JL, Gursel T, Ingerslev J, Goodeve AC, Peake IR, Daly ME. A novel von Willebrand disease-causing mutation (Arg273Trp) in the von Willebrand factor propeptide that results in defective multimerization and secretion. Blood. 2000 Jul 15;96(2):560-8. PMID:10887119
- ↑ Bodo I, Katsumi A, Tuley EA, Eikenboom JC, Dong Z, Sadler JE. Type 1 von Willebrand disease mutation Cys1149Arg causes intracellular retention and degradation of heterodimers: a possible general mechanism for dominant mutations of oligomeric proteins. Blood. 2001 Nov 15;98(10):2973-9. PMID:11698279
Categories: Homo sapiens | Diener, J L. | Fremont, D H. | Huang, R H. | Sadler, J E. | Schaub, R G. | Aptamer | Arc1772 | Arc1779 | Blood clotting-blood clotting regulator complex | Blood coagulation | Cell adhesion | Cleavage on pair of basic residue | Disease mutation | Disulfide bond | Extracellular matrix | Glycoprotein | Hemostasis | Isopeptide bond | Platelet glycoprotein ib | Secreted | Von willebrand disease | Vwf
