2a2x: Difference between revisions

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-{{Seed}}
-[[Image:2a2x.png|left|200px]]
-<!--
+==Orally Active Thrombin Inhibitors in Complex with Thrombin Inh12==
-The line below this paragraph, containing "STRUCTURE_2a2x", creates the "Structure Box" on the page.
+<StructureSection load='2a2x' size='340' side='right'caption='[[2a2x]], [[Resolution|resolution]] 2.44&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2a2x]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A2X FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.44&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALC:2-AMINO-3-CYCLOHEXYL-PROPIONIC+ACID'>ALC</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NA9:N-(CARBOXYMETHYL)-3-CYCLOHEXYL-D-ALANYL-N-({6-[AMINO(IMINO)METHYL]PYRIDIN-3-YL}METHYL)-N~2~-METHYL-L-ALANINAMIDE'>NA9</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=SMF:4-SULFOMETHYL-L-PHENYLALANINE'>SMF</scene></td></tr>
-{{STRUCTURE_2a2x|  PDB=2a2x  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2a2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a2x OCA], [https://pdbe.org/2a2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a2x RCSB], [https://www.ebi.ac.uk/pdbsum/2a2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a2x ProSAT]</span></td></tr>
+</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/a2/2a2x_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=2a2x ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Synthesis and SAR of orally active thrombin inhibitors of the d-Phe-Pro-Arg type with focus on the P2-moiety are described. The unexpected increase in in vitro potency, oral bioavailability, and in vivo activity of inhibitors with dehydroproline as P2-isostere is discussed. Over a period of 24h the antithrombin activity of the most active inhibitors with IC(50)s in the nanomolar range was determined in dogs demonstrating high thrombin inhibitory activity in plasma and an appropriate duration of action after oral administration.
-===Orally Active Thrombin Inhibitors in Complex with Thrombin Inh12===
+Orally active thrombin inhibitors. Part 2: optimization of the P2-moiety.,Lange UE, Baucke D, Hornberger W, Mack H, Seitz W, Hoffken HW Bioorg Med Chem Lett. 2006 May 15;16(10):2648-53. Epub 2006 Feb 3. PMID:16460939<ref>PMID:16460939</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2a2x" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_16460939}}, adds the Publication Abstract to the page
+*[[Thrombin 3D Structures|Thrombin 3D Structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 16460939 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16460939}}
+__TOC__
+</StructureSection>
-==About this Structure==
-A2X is a 3 chains structure of sequences 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=2A2X OCA].
-==Reference==
-<ref group="xtra">PMID:16460939</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Thrombin]]
+[[Category: Large Structures]]
-[[Category: Baucke, D.]]
+[[Category: Synthetic construct]]
-[[Category: Hoeffken, H W.]]
+[[Category: Baucke D]]
-[[Category: Hornberger, W.]]
+[[Category: Hoeffken HW]]
-[[Category: Lange, U E.W.]]
+[[Category: Hornberger W]]
-[[Category: Mack, H.]]
+[[Category: Lange UEW]]
-[[Category: Seitz, W.]]
+[[Category: Mack H]]
-[[Category: Blood clotting]]
+[[Category: Seitz W]]
-[[Category: Serine protease]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 10:33:55 2009''