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[[Image:1dx5.png|left|200px]]


{{STRUCTURE_1dx5|  PDB=1dx5  |  SCENE=  }}
==Crystal structure of the thrombin-thrombomodulin complex==
 
<StructureSection load='1dx5' size='340' side='right'caption='[[1dx5]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
===Crystal structure of the thrombin-thrombomodulin complex===
== Structural highlights ==
 
<table><tr><td colspan='2'>[[1dx5]] is a 12 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=1DX5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DX5 FirstGlance]. <br>
{{ABSTRACT_PUBMED_10761923}}
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GJ:L-ALPHA-GLUTAMYL-N-{(1S)-4-{[AMINO(IMINIO)METHYL]AMINO}-1-[(1S)-2-CHLORO-1-HYDROXYETHYL]BUTYL}GLYCINAMIDE'>0GJ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
==About this Structure==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1dx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dx5 OCA], [https://pdbe.org/1dx5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dx5 RCSB], [https://www.ebi.ac.uk/pdbsum/1dx5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dx5 ProSAT]</span></td></tr>
[[1dx5]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DX5 OCA].  
</table>
== Disease ==
[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>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dx/1dx5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1dx5 ConSurf].
<div style="clear:both"></div>


==See Also==
==See Also==
*[[Thrombin|Thrombin]]
*[[Thrombin 3D Structures|Thrombin 3D Structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:010761923</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Thrombin]]
[[Category: Large Structures]]
[[Category: Bode, W.]]
[[Category: Bode W]]
[[Category: Fuentes-Prior, P.]]
[[Category: Fuentes-Prior P]]
[[Category: Huber, R.]]
[[Category: Huber R]]
[[Category: Iwanaga, Y.]]
[[Category: Iwanaga Y]]
[[Category: Light, D R.]]
[[Category: Light DR]]
[[Category: Morser, J.]]
[[Category: Morser J]]
[[Category: Pagila, R.]]
[[Category: Pagila R]]
[[Category: Rumennik, G.]]
[[Category: Rumennik G]]
[[Category: Seto, M.]]
[[Category: Seto M]]
[[Category: Anticoagulant complex]]
[[Category: Antifibrinolytic complex]]
[[Category: Egf-like domain]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Serine proteinase]]

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