1nt1: Difference between revisions

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-{{Seed}}
-[[Image:1nt1.png|left|200px]]
-<!--
+==thrombin in complex with selective macrocyclic inhibitor==
-The line below this paragraph, containing "STRUCTURE_1nt1", creates the "Structure Box" on the page.
+<StructureSection load='1nt1' size='340' side='right'caption='[[1nt1]], [[Resolution|resolution]] 2.00&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'>[[1nt1]] is a 2 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=1NT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NT1 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&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T76:(6R,21AS)-17-CHLORO-6-CYCLOHEXYL-2,3,6,7,10,11,19,20-OCTAHYDRO-1H,5H-PYRROLO[1,2-K][1,4,8,11,14]BENZOXATETRAAZA-CYCLOHEPTADECINE-5,8,12,21(9H,13H,21AH)-TETRONE'>T76</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-{{STRUCTURE_1nt1|  PDB=1nt1  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nt1 OCA], [https://pdbe.org/1nt1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nt1 RCSB], [https://www.ebi.ac.uk/pdbsum/1nt1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nt1 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/nt/1nt1_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1nt1 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.
-===thrombin in complex with selective macrocyclic inhibitor===
+Design and synthesis of potent and selective macrocyclic thrombin inhibitors.,Nantermet PG, Barrow JC, Newton CL, Pellicore JM, Young M, Lewis SD, Lucas BJ, Krueger JA, McMasters DR, Yan Y, Kuo LC, Vacca JP, Selnick HG Bioorg Med Chem Lett. 2003 Aug 18;13(16):2781-4. PMID:12873514<ref>PMID:12873514</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1nt1" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_12873514}}, adds the Publication Abstract to the page
+*[[Hirudin 3D structures|Hirudin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 12873514 is the PubMed ID number.
+*[[Thrombin 3D Structures|Thrombin 3D Structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_12873514}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-NT1 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=1NT1 OCA].
+[[Category: Hirudo medicinalis]]
-==Reference==
-Design and synthesis of potent and selective macrocyclic thrombin inhibitors., Nantermet PG, Barrow JC, Newton CL, Pellicore JM, Young M, Lewis SD, Lucas BJ, Krueger JA, McMasters DR, Yan Y, Kuo LC, Vacca JP, Selnick HG, Bioorg Med Chem Lett. 2003 Aug 18;13(16):2781-4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12873514 12873514]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Thrombin]]
+[[Category: Barrow JC]]
-[[Category: Barrow, J C.]]
+[[Category: Krueger JA]]
-[[Category: Krueger, J A.]]
+[[Category: Kuo LC]]
-[[Category: Kuo, L C.]]
+[[Category: Lewis SD]]
-[[Category: Lewis, S D.]]
+[[Category: Lucas BJ]]
-[[Category: Lucas, B J.]]
+[[Category: McMasters DR]]
-[[Category: McMasters, D R.]]
+[[Category: Nantermet PG]]
-[[Category: Nantermet, P G.]]
+[[Category: Newton CL]]
-[[Category: Newton, C L.]]
+[[Category: Pellicore JM]]
-[[Category: Pellicore, J M.]]
+[[Category: Selnick HG]]
-[[Category: Selnick, H G.]]
+[[Category: Vacca JP]]
-[[Category: Vacca, J P.]]
+[[Category: Yan Y]]
-[[Category: Yan, Y.]]
+[[Category: Young M]]
-[[Category: Young, M.]]
-[[Category: Thrombin inhibitor complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:58:38 2008''