1zom: Difference between revisions

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-[[Image:1zom.png|left|200px]]
-{{STRUCTURE_1zom|  PDB=1zom  |  SCENE=  }}
+==Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor==
+<StructureSection load='1zom' size='340' side='right'caption='[[1zom]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1zom]] is a 1 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=1ZOM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZOM FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=339:(S)-2-(3-((R)-1-(4-BROMOPHENYL)ETHYL)UREIDO)-N-((S)-1-((S)-5-GUANIDINO-1-OXO-1-(THIAZOL-2-YL)PENTAN-2-YLAMINO)-3-METHYL-1-OXOBUTAN-2-YL)-5-UREIDOPENTANAMIDE'>339</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1zom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zom OCA], [https://pdbe.org/1zom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zom RCSB], [https://www.ebi.ac.uk/pdbsum/1zom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zom ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://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 ==
+[https://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.
+== 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/zo/1zom_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=1zom ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selective peptidomimetic inhibitors of FXIa were designed and synthesized. Some of these inhibitors showed low nanomolar FXIa inhibitory activity with &gt;1000-fold FXa selectivity and &gt;100-fold thrombin selectivity. The X-ray structure of one of these inhibitors, 36, demonstrates its unique binding interactions with FXIa. Compound 32 caused a doubling of the activated partial thromboplastin time in human plasma at 2.4 microM and was efficacious in a rat model of venous thrombosis. These data suggest that factor XIa plays a significant role in venous thrombosis and may be a suitable target for the development of antithrombotic therapy.
-===Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor===
+Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants.,Lin J, Deng H, Jin L, Pandey P, Quinn J, Cantin S, Rynkiewicz MJ, Gorga JC, Bibbins F, Celatka CA, Nagafuji P, Bannister TD, Meyers HV, Babine RE, Hayward NJ, Weaver D, Benjamin H, Stassen F, Abdel-Meguid SS, Strickler JE J Med Chem. 2006 Dec 28;49(26):7781-91. PMID:17181160<ref>PMID:17181160</ref>
-{{ABSTRACT_PUBMED_17181160}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1zom" style="background-color:#fffaf0;"></div>
-[[1zom]] is a 1 chain structure of [[Factor XIa]] with sequence 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=1ZOM OCA].
 ==See Also==
-*[[Factor XIa|Factor XIa]]
+*[[Factor XIa 3D structures|Factor XIa 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:017181160</ref><references group="xtra"/>
+__TOC__
-[[Category: Coagulation factor XIa]]
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bibbins, F.]]
+[[Category: Large Structures]]
-[[Category: Cantin, S.]]
+[[Category: Bibbins F]]
-[[Category: Deng, H.]]
+[[Category: Cantin S]]
-[[Category: Gorga, J.]]
+[[Category: Deng H]]
-[[Category: Jin, L.]]
+[[Category: Gorga J]]
-[[Category: Lin, J.]]
+[[Category: Jin L]]
-[[Category: Magee, S.]]
+[[Category: Lin J]]
-[[Category: Pandey, P.]]
+[[Category: Magee S]]
-[[Category: Quinn, J.]]
+[[Category: Pandey P]]
-[[Category: Rynkiewicz, M.]]
+[[Category: Quinn J]]
-[[Category: Fxia]]
+[[Category: Rynkiewicz M]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor]]