5tno: Difference between revisions

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-'''Unreleased structure'''
-The entry 5tno is ON HOLD  until Paper Publication
+==Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors==
+<StructureSection load='5tno' size='340' side='right' caption='[[5tno]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5tno]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TNO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TNO FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tnt|5tnt]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_IXa Coagulation factor IXa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.22 3.4.21.22] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tno OCA], [http://pdbe.org/5tno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tno RCSB], [http://www.ebi.ac.uk/pdbsum/5tno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tno ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[http://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:[http://omim.org/entry/300807 300807]]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref>
+== Function ==
+[[http://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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Using structure based drug design, novel aminobenzisoxazoles as coagulation factor IXa inhibitors were designed and synthesized. Highly selective inhibition of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK) profiles were also evaluated.
-Authors:
+Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa inhibitors.,Sakurada I, Endo T, Hikita K, Hirabayashi T, Hosaka Y, Kato Y, Maeda Y, Matsumoto S, Mizuno T, Nagasue H, Nishimura T, Shimada S, Shinozaki M, Taguchi K, Takeuchi K, Yokoyama T, Hruza A, Reichert P, Zhang T, Wood HB, Nakao K, Furusako S Bioorg Med Chem Lett. 2017 Mar 6. pii: S0960-894X(17)30225-1. doi:, 10.1016/j.bmcl.2017.03.002. PMID:28408226<ref>PMID:28408226</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5tno" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Coagulation factor IXa]]
+[[Category: Endo, T]]
+[[Category: Furusako, S]]
+[[Category: Hikita, K]]
+[[Category: Hirabayashi, T]]
+[[Category: Hosaka, Y]]
+[[Category: Hruza, A]]
+[[Category: Kato, Y]]
+[[Category: Maeda, Y]]
+[[Category: Matsumoto, S]]
+[[Category: Mizuno, T]]
+[[Category: Nagasue, H]]
+[[Category: Nakao, K]]
+[[Category: Nishimura, T]]
+[[Category: Reichert, P]]
+[[Category: Sakurada, I]]
+[[Category: Shimada, S]]
+[[Category: Shinozaki, M]]
+[[Category: Taguchi, K]]
+[[Category: Takeuchi, K]]
+[[Category: Wood, H B]]
+[[Category: Yokoyama, T]]
+[[Category: Zhang, T]]
+[[Category: Blood coagulation]]
+[[Category: Coagulation factor]]
+[[Category: Hydrolase inhibitor complex]]
+[[Category: Hydrolase-2]]
+[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Serine proteinase]]