3lc3: Difference between revisions

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-{{Seed}}
-[[Image:3lc3.jpg|left|200px]]
-<!--
+==Benzothiophene Inhibitors of Factor IXa==
-The line below this paragraph, containing "STRUCTURE_3lc3", creates the "Structure Box" on the page.
+<StructureSection load='3lc3' size='340' side='right'caption='[[3lc3]], [[Resolution|resolution]] 1.90&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'>[[3lc3]] is a 4 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=3LC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LC3 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]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IYX:1-[5-(3,4-DIMETHOXYPHENYL)-1-BENZOTHIOPHEN-2-YL]METHANEDIAMINE'>IYX</scene></td></tr>
-{{STRUCTURE_3lc3|  PDB=3lc3  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3lc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lc3 OCA], [https://pdbe.org/3lc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lc3 RCSB], [https://www.ebi.ac.uk/pdbsum/3lc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lc3 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[https://omim.org/entry/306900 306900]; also known as Christmas disease.<ref>PMID:8295821</ref> <ref>PMID:2592373</ref> <ref>PMID:2743975</ref> <ref>PMID:6603618</ref> <ref>PMID:3009023</ref> <ref>PMID:3790720</ref> <ref>PMID:3401602</ref> <ref>PMID:3243764</ref> <ref>PMID:2713493</ref> <ref>PMID:2714791</ref> <ref>PMID:2773937</ref> <ref>PMID:2775660</ref> <ref>PMID:2753873</ref> <ref>PMID:2738071</ref> <ref>PMID:2472424</ref> <ref>PMID:2339358</ref> <ref>PMID:2372509</ref> <ref>PMID:2162822</ref> <ref>PMID:1958666</ref> <ref>PMID:1902289</ref> <ref>PMID:1346975</ref> <ref>PMID:1615485</ref> <ref>PMID:8257988</ref> <ref>PMID:8076946</ref> <ref>PMID:8199596</ref> <ref>PMID:7981722</ref> <ref>PMID:8680410</ref> <ref>PMID:9222764</ref> <ref>PMID:9590153</ref> <ref>PMID:9452115</ref> <ref>PMID:9600455</ref> <ref>PMID:10698280</ref> <ref>PMID:10094553</ref> <ref>PMID:11122099</ref> <ref>PMID:12588353</ref> <ref>PMID:12604421</ref>   Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide.  Defects in F9 are the cause of thrombophilia due to factor IX defect (THPH8) [MIM:[https://omim.org/entry/300807 300807]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN] Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
+== 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/lc/3lc3_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=3lc3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+FIXa is a serine protease enzyme involved in the intrinsic pathway of the coagulation cascade. The upstream intervention of the coagulation cascade in selectively inhibiting FIXa would leave hemostasis intact via the extrinsic pathway, leading to an optimum combination of efficacy and safety with low incidence of bleeding. We have identified 2-amindinobenzothiophene template as a lead scaffold for FIXa inhibiton based on its homology with urokinase plasminogen activator (uPA). Subsequent SAR work on the template revealed a number of highly potent FIXa inhibitors, though with moderate selectivity against FXa. X-ray study with one of the analogues demonstrated active site binding interaction with the induced opening of the S1 beta pocket and a secondary binding at the S2-S4 sites, which is in direct contrast with the previous finding.
-===Benzothiophene Inhibitors of Factor IXa===
+Studies of Benzothiophene Template as Potent Factor IXa (FIXa) Inhibitors in Thrombosis.,Wang S, Beck R, Blench T, Burd A, Buxton S, Malic M, Ayele T, Shaikh S, Chahwala S, Chander C, Holland R, Merette S, Zhao L, Blackney M, Watts A J Med Chem. 2010 Feb 25;53(4):1465-72. PMID:20121198<ref>PMID:20121198</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3lc3" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20121198}}, adds the Publication Abstract to the page
+*[[Factor IX|Factor IX]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20121198 is the PubMed ID number.
+*[[Factor IX 3D structures|Factor IX 3D structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_20121198}}
+<references/>
+__TOC__
-==Disease==
+</StructureSection>
-Known disease associated with this structure: Hemophilia B OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300746 300746]]
-==About this Structure==
-LC3 is a 4 chains structure with 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=3LC3 OCA].
-==Reference==
-<ref group="xtra">PMID:20121198</ref><references group="xtra"/>
-[[Category: Coagulation factor IXa]]
 [[Category: Homo sapiens]]
-[[Category: Beck, R.]]
+[[Category: Large Structures]]
-[[Category: Wang, S.]]
+[[Category: Beck R]]
-[[Category: Blood coagulation]]
+[[Category: Wang S]]
-[[Category: Calcium]]
-[[Category: Cleavage on pair of basic residue]]
-[[Category: Disease mutation]]
-[[Category: Disulfide bond]]
-[[Category: Egf-like domain]]
-[[Category: Gamma-carboxyglutamic acid]]
-[[Category: Glycoprotein]]
-[[Category: Hemophilia]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Hydroxylation]]
-[[Category: Peptidase s1]]
-[[Category: Pharmaceutical]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Protease]]
-[[Category: Protein-inhibitor complex]]
-[[Category: Secreted]]
-[[Category: Serine protease]]
-[[Category: Sulfation]]
-[[Category: Zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 25 13:27:22 2010''