2p3t: Difference between revisions

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-{{Seed}}
-[[Image:2p3t.png|left|200px]]
-<!--
+==Crystal structure of human factor XA complexed with 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide==
-The line below this paragraph, containing "STRUCTURE_2p3t", creates the "Structure Box" on the page.
+<StructureSection load='2p3t' size='340' side='right'caption='[[2p3t]], [[Resolution|resolution]] 1.92&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'>[[2p3t]] is a 2 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=2P3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P3T 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]] 1.92&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=993:3-CHLORO-4-(2-METHYLAMINO-IMIDAZOL-1-YLMETHYL)-THIOPHENE-2-CARBOXYLIC+ACID+[4-CHLORO-2-(5-CHLORO-PYRIDIN-2-YLCARBAMOYL)-6-METHOXY-PHENYL]-AMIDE'>993</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-{{STRUCTURE_2p3t|  PDB=2p3t  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p3t OCA], [https://pdbe.org/2p3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p3t RCSB], [https://www.ebi.ac.uk/pdbsum/2p3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p3t ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
+== 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/p3/2p3t_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=2p3t ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the subject of intensive drug discovery efforts. Investigation of a hit from high-throughput screening identified a series of thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation of hydrophilic groups led to the discovery of compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant activity. Based on their high potency, selectivity, oral pharmacokinetics, and efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b), ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.
-===Crystal structure of human factor XA complexed with 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide===
+Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors(1).,Ye B, Arnaiz DO, Chou YL, Griedel BD, Karanjawala R, Lee W, Morrissey MM, Sacchi KL, Sakata ST, Shaw KJ, Wu SC, Zhao Z, Adler M, Cheeseman S, Dole WP, Ewing J, Fitch R, Lentz D, Liang A, Light D, Morser J, Post J, Rumennik G, Subramanyam B, Sullivan ME, Vergona R, Walters J, Wang YX, White KA, Whitlow M, Kochanny MJ J Med Chem. 2007 Jun 28;50(13):2967-80. Epub 2007 May 31. PMID:17536795<ref>PMID:17536795</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2p3t" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17536795}}, adds the Publication Abstract to the page
+*[[Factor Xa|Factor Xa]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17536795 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17536795}}
+__TOC__
+</StructureSection>
-==About this Structure==
-P3T is a [[Protein complex]] 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=2P3T OCA].
-==Reference==
-Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors(1)., Ye B, Arnaiz DO, Chou YL, Griedel BD, Karanjawala R, Lee W, Morrissey MM, Sacchi KL, Sakata ST, Shaw KJ, Wu SC, Zhao Z, Adler M, Cheeseman S, Dole WP, Ewing J, Fitch R, Lentz D, Liang A, Light D, Morser J, Post J, Rumennik G, Subramanyam B, Sullivan ME, Vergona R, Walters J, Wang YX, White KA, Whitlow M, Kochanny MJ, J Med Chem. 2007 Jun 28;50(13):2967-80. Epub 2007 May 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17536795 17536795]
-[[Category: Coagulation factor Xa]]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Adler, M.]]
+[[Category: Adler M]]
-[[Category: Whitlow, M.]]
+[[Category: Whitlow M]]
-[[Category: Blood clotting]]
-[[Category: Coagulation cofactor]]
-[[Category: Nonamidine]]
-[[Category: Protease]]
-[[Category: Protein inhibitor complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:56:46 2008''