2jh0: Difference between revisions

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-[[Image:2jh0.jpg|left|200px]]<br /><applet load="2jh0" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2jh0, resolution 1.70&Aring;" />
-'''HUMAN THROMBIN HIRUGEN INHIBITOR COMPLEX.'''<br />
-==Disease==
+==Human Thrombin Hirugen Inhibitor complex==
-Known diseases associated with this structure: Dysprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hyperprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hypoprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]]
+<StructureSection load='2jh0' size='340' side='right'caption='[[2jh0]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2jh0]] is a 3 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=2JH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JH0 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=701:(2R)-2-(5-CHLORO-2-THIENYL)-N-{(3S)-1-[(1S)-1-METHYL-2-MORPHOLIN-4-YL-2-OXOETHYL]-2-OXOPYRROLIDIN-3-YL}PROPENE-1-SULFONAMIDE'>701</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2jh5|2jh5]], [[2jh6|2jh6]]</div></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jh0 OCA], [https://pdbe.org/2jh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jh0 RCSB], [https://www.ebi.ac.uk/pdbsum/2jh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jh0 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>  [[https://www.uniprot.org/uniprot/HIR3A_HIRME HIR3A_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.
+== 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/jh/2jh0_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=2jh0 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Structure-based design (SBD) is a challenging endeavour since even localised SAR can hardly ever be explained by the variation of just one dominating factor. Here, we present a rare example where structural information combined with ab initio calculations clearly indicate that the observed difference in biological activity is dominated by conformational effects. The learnings discussed are successfully put to the test and have the potential to be of general use as a qualitative guide in SBD efforts.
-==About this Structure==
+Sulfonamide-related conformational effects and their importance in structure-based design.,Senger S, Chan C, Convery MA, Hubbard JA, Shah GP, Watson NS, Young RJ Bioorg Med Chem Lett. 2007 May 15;17(10):2931-4. Epub 2007 Feb 16. PMID:17336062<ref>PMID:17336062</ref>
-JH0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=701:'>701</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Known structural/functional Site: <scene name='pdbsite=AC1:Na+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JH0 OCA].
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2jh0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Hirudin 3D structures|Hirudin 3D structures]]
+*[[Thrombin 3D Structures|Thrombin 3D Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
 [[Category: Thrombin]]
-[[Category: Chan, C.]]
+[[Category: Chan, C]]
-[[Category: Convery, M A.]]
+[[Category: Convery, M A]]
-[[Category: Hubbard, J A.]]
+[[Category: Hubbard, J A]]
-[[Category: Senger, S.]]
+[[Category: Senger, S]]
-[[Category: Shah, G P.]]
+[[Category: Shah, G P]]
-[[Category: Watson, N S.]]
+[[Category: Watson, N S]]
-[[Category: Young, R J.]]
+[[Category: Young, R J]]
-[[Category: 701]]
+[[Category: Acute phase]]
-[[Category: CA]]
+[[Category: Blood coagulation]]
-[[Category: NA]]
+[[Category: Disease mutation]]
-[[Category: acute phase]]
+[[Category: Gamma-carboxyglutamic acid]]
-[[Category: blood coagulation]]
+[[Category: Glycoprotein]]
-[[Category: calcium]]
+[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: disease mutation]]
+[[Category: Kringle]]
-[[Category: gamma-carboxyglutamic acid]]
+[[Category: Protease]]
-[[Category: glycoprotein]]
+[[Category: Protease inhibitor]]
-[[Category: hydrolase]]
+[[Category: Serine protease]]
-[[Category: inhibitor]]
+[[Category: Serine protease inhibitor]]
-[[Category: kringle]]
+[[Category: Sulfation]]
-[[Category: polymorphism]]
+[[Category: Zymogen]]
-[[Category: protease]]
-[[Category: protease inhibitor]]
-[[Category: serine protease]]
-[[Category: serine protease inhibitor]]
-[[Category: sulfation]]
-[[Category: thrombin]]
-[[Category: zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:03:11 2008''