1e0f

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[[Image:1e0f.png|left|200px]]
 
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==Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor==
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The line below this paragraph, containing "STRUCTURE_1e0f", creates the "Structure Box" on the page.
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<StructureSection load='1e0f' size='340' side='right'caption='[[1e0f]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[1e0f]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemadipsa_sylvestris Haemadipsa sylvestris] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E0F 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]] 3.1&#8491;</td></tr>
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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=1e0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e0f OCA], [https://pdbe.org/1e0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e0f RCSB], [https://www.ebi.ac.uk/pdbsum/1e0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e0f ProSAT]</span></td></tr>
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{{STRUCTURE_1e0f| PDB=1e0f | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e0/1e0f_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1e0f ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The serine proteinase alpha-thrombin plays a pivotal role in the regulation of blood fluidity, and therefore constitutes a primary target in the treatment of various haemostatic disorders. Haemadin is a slow tight- binding thrombin inhibitor from the land-living leech Haemadipsa sylvestris. Here we present the 3.1 A crystal structure of the human alpha-thrombin- haemadin complex. The N-terminal segment of haemadin binds to the active site of thrombin, forming a parallel beta-strand with residues Ser214-Gly216 of the proteinase. This mode of binding is similar to that observed in another leech-derived inhibitor, hirudin. In contrast to hirudin, however, the markedly acidic C-terminal peptide of haemadin does not bind the fibrinogen-recognition exosite, but interacts with the heparin-binding exosite of thrombin. Thus, haemadin binds to thrombin according to a novel mechanism, despite an overall structural similarity with hirudin. Haemadin inhibits both free and thrombomodulin-bound alpha-thrombin, but not intermediate activation forms such as meizothrombin. This specific anticoagulant ability of haemadin makes it an ideal candidate for an antithrombotic agent, as well as a starting point for the design of novel antithrombotics.
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===CRYSTAL STRUCTURE OF THE HUMAN ALPHA-THROMBIN-HAEMADIN COMPLEX: AN EXOSITE II-BINDING INHIBITOR===
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Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor.,Richardson JL, Kroger B, Hoeffken W, Sadler JE, Pereira P, Huber R, Bode W, Fuentes-Prior P EMBO J. 2000 Nov 1;19(21):5650-60. PMID:11060016<ref>PMID:11060016</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 1e0f" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_11060016}}, adds the Publication Abstract to the page
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 11060016 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_11060016}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1E0F is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Haemadipsa_sylvestris Haemadipsa sylvestris] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E0F OCA].
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==Reference==
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Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor., Richardson JL, Kroger B, Hoeffken W, Sadler JE, Pereira P, Huber R, Bode W, Fuentes-Prior P, EMBO J. 2000 Nov 1;19(21):5650-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11060016 11060016]
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[[Category: Haemadipsa sylvestris]]
[[Category: Haemadipsa sylvestris]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Thrombin]]
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[[Category: Bode W]]
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[[Category: Bode, W.]]
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[[Category: Fuentes-Prior P]]
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[[Category: Fuentes-Prior, P.]]
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[[Category: Hoefken W]]
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[[Category: Hoefken, W.]]
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[[Category: Huber R]]
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[[Category: Huber, R.]]
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[[Category: Kroeger B]]
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[[Category: Kroeger, B.]]
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[[Category: Pereira P]]
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[[Category: Pereira, P.]]
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[[Category: Richardson JL]]
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[[Category: Richardson, J.]]
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[[Category: Coagulation/crystal structure/heparin-binding site/ hirudin/thrombin inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:56:03 2008''
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Current revision

Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor

PDB ID 1e0f

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