1fpc

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{{Seed}}
 
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[[Image:1fpc.png|left|200px]]
 
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==ACTIVE SITE MIMETIC INHIBITION OF THROMBIN==
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The line below this paragraph, containing "STRUCTURE_1fpc", creates the "Structure Box" on the page.
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<StructureSection load='1fpc' size='340' side='right'caption='[[1fpc]], [[Resolution|resolution]] 2.30&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'>[[1fpc]] 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=1FPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FPC FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.3&#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=0ZI:AMINO{[(4S)-4-({[5-(DIMETHYLAMINO)NAPHTHALEN-1-YL]SULFONYL}AMINO)-5-(4-ETHYLPIPERIDIN-1-YL)-5-OXOPENTYL]AMINO}METHANIMINIUM'>0ZI</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
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{{STRUCTURE_1fpc| PDB=1fpc | SCENE= }}
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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=1fpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fpc OCA], [https://pdbe.org/1fpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fpc RCSB], [https://www.ebi.ac.uk/pdbsum/1fpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fpc ProSAT]</span></td></tr>
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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/fp/1fpc_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=1fpc 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 structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed.
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===ACTIVE SITE MIMETIC INHIBITION OF THROMBIN===
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Active-site mimetic inhibition of thrombin.,Mathews II, Tulinsky A Acta Crystallogr D Biol Crystallogr. 1995 Jul 1;51(Pt 4):550-9. PMID:15299843<ref>PMID:15299843</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 1fpc" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15299843}}, adds the Publication Abstract to the page
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*[[Hirudin 3D structures|Hirudin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15299843 is the PubMed ID number.
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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== References ==
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{{ABSTRACT_PUBMED_15299843}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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1FPC is a [[Single protein]] structure of 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=1FPC OCA].
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[[Category: Hirudo medicinalis]]
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==Reference==
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Active-site mimetic inhibition of thrombin., Mathews II, Tulinsky A, Acta Crystallogr D Biol Crystallogr. 1995 Jul 1;51(Pt 4):550-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15299843 15299843]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Thrombin]]
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[[Category: Mathews II]]
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[[Category: Mathews, I I.]]
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[[Category: Tulinsky A]]
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[[Category: Tulinsky, A.]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:43:52 2008''
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Current revision

ACTIVE SITE MIMETIC INHIBITION OF THROMBIN

PDB ID 1fpc

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