3d49

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{{STRUCTURE_3d49| PDB=3d49 | SCENE= }}
 
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===Thrombin Inhibition===
 
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{{ABSTRACT_PUBMED_019409395}}
 
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==Disease==
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==Thrombin Inhibition==
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[[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://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:[http://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:[http://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:[http://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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<StructureSection load='3d49' size='340' side='right'caption='[[3d49]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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==Function==
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<table><tr><td colspan='2'>[[3d49]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] 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=3D49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D49 FirstGlance]. <br>
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[[http://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> [[http://www.uniprot.org/uniprot/ITH1_HIRME ITH1_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.<ref>PMID:17585879</ref>
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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]] 1.5&#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=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
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==About this Structure==
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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=3d49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d49 OCA], [https://pdbe.org/3d49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d49 RCSB], [https://www.ebi.ac.uk/pdbsum/3d49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d49 ProSAT]</span></td></tr>
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[[3d49]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] 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=3D49 OCA].
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HIRV1_HIRME HIRV1_HIRME] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.<ref>PMID:17585879</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/d4/3d49_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=3d49 ConSurf].
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<div style="clear:both"></div>
==See Also==
==See Also==
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*[[Hirudin|Hirudin]]
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*[[Hirudin 3D structures|Hirudin 3D structures]]
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*[[Thrombin|Thrombin]]
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019409395</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Hirudo medicinalis]]
[[Category: Hirudo medicinalis]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Thrombin]]
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[[Category: Large Structures]]
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[[Category: Baum, B.]]
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[[Category: Baum B]]
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[[Category: Heine, A.]]
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[[Category: Heine A]]
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[[Category: Klebe, G.]]
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[[Category: Klebe G]]
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[[Category: Acute phase]]
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[[Category: Blood clotting-hydrolase inhibitor complex]]
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[[Category: Blood clotting/hydrolase inhibitor]]
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[[Category: Blood coagulation]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Disease mutation]]
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[[Category: Gamma-carboxyglutamic acid]]
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[[Category: Glycoprotein]]
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[[Category: Kringle]]
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[[Category: Protease]]
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[[Category: Secreted]]
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[[Category: Serine protease]]
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[[Category: Zymogen]]
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Current revision

Thrombin Inhibition

PDB ID 3d49

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