4ty7: Difference between revisions

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-'''Unreleased structure'''
+==Factor XIa in complex with the inhibitor (2S)-6-amino-N-{(1S)-1-[4-(3-amino-2H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-2-ethylhexanamide==
+<StructureSection load='4ty7' size='340' side='right' caption='[[4ty7]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ty7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TY7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TY7 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=39F:(2S)-6-AMINO-N-{(1S)-1-[4-(3-AMINO-2H-INDAZOL-6-YL)-5-CHLORO-1H-IMIDAZOL-2-YL]-2-PHENYLETHYL}-2-ETHYLHEXANAMIDE'>39F</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </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=4ty7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ty7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ty7 RCSB], [http://www.ebi.ac.uk/pdbsum/4ty7 PDBsum]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[http://omim.org/entry/612416 612416]]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine core have been optimized to provide compound 16b, a potent, reversible inhibitor of FXIa (Ki = 0.3 nM) having in vivo antithrombotic efficacy in the rabbit AV-shunt thrombosis model (ID50 = 0.6 mg/kg + 1 mg kg-1 h-1). Initial analog selection was informed by molecular modeling using compounds 11a and 11h overlaid onto the X-ray crystal structure of tetrahydroquinoline 3 complexed to FXIa. Further optimization was achieved by specific modifications derived from careful analysis of the X-ray crystal structure of the FXIa/11h complex. Compound 16b was well tolerated and enabled extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.
-The entry 4ty7 is ON HOLD  until Paper Publication
+Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity.,Hangeland JJ, Friends TJ, Rossi KA, Smallheer JM, Wang C, Sun Z, Corte JR, Fang T, Wong PC, Rendina AR, Barbera FA, Bozarth JM, Luettgen JM, Watson CA, Zhang G, Wei A, Ramamurthy V, Morin PE, Bisacchi GS, Subramaniam S, Arunachalam P, Mathur A, Seiffert DA, Wexler RR, Quan ML J Med Chem. 2014 Dec 2. PMID:25405503<ref>PMID:25405503</ref>
-Authors: Wei, A.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Factor XIa in complex with the inhibitor (2S)-6-amino-N-{(1S)-1-[4-(3-amino-2H-indazol-6-yl)-5-chloro-1H-imidazol-2-yl]-2-phenylethyl}-2-ethylhexanamide
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Coagulation factor XIa]]
+[[Category: Wei, A]]
+[[Category: Blood coagulation factor]]
+[[Category: Hydrolase]]
+[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Protein inhibitor complex]]
+[[Category: Serine protease]]