1zlr

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(New page: 200px<br /> <applet load="1zlr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zlr, resolution 2.50&Aring;" /> '''Factor XI catalytic...)
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[[Image:1zlr.gif|left|200px]]<br />
 
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<applet load="1zlr" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zlr, resolution 2.50&Aring;" />
 
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'''Factor XI catalytic domain complexed with 2-guanidino-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl nicotinate'''<br />
 
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==Overview==
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==Factor XI catalytic domain complexed with 2-guanidino-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl nicotinate==
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A series of functionalized aryl boronic acids were synthesized and, evaluated as potential inhibitors of factor XIa. Crystal structures of the, protein-inhibitor complexes led to the design and synthesis of second, generation compounds showing single digit micromolar inhibition against, FXIa and selectivity against thrombin, trypsin, and FXa.
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<StructureSection load='1zlr' size='340' side='right'caption='[[1zlr]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1zlr]] 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=1ZLR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZLR FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=368:(1R)-2-{[AMINO(IMINO)METHYL]AMINO}-1-{4-[(4R)-4-(HYDROXYMETHYL)-1,3,2-DIOXABOROLAN-2-YL]PHENYL}ETHYL+NICOTINATE'>368</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zlr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zlr OCA], [https://pdbe.org/1zlr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zlr RCSB], [https://www.ebi.ac.uk/pdbsum/1zlr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zlr ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zl/1zlr_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1zlr ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A series of functionalized aryl boronic acids were synthesized and evaluated as potential inhibitors of factor XIa. Crystal structures of the protein-inhibitor complexes led to the design and synthesis of second generation compounds showing single digit micromolar inhibition against FXIa and selectivity against thrombin, trypsin, and FXa.
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==Disease==
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Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa.,Lazarova TI, Jin L, Rynkiewicz M, Gorga JC, Bibbins F, Meyers HV, Babine R, Strickler J Bioorg Med Chem Lett. 2006 Oct 1;16(19):5022-7. Epub 2006 Jul 28. PMID:16876411<ref>PMID:16876411</ref>
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Known diseases associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]], Factor XI deficiency, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1ZLR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, 368 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZLR OCA].
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</div>
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<div class="pdbe-citations 1zlr" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Synthesis and in vitro biological evaluation of aryl boronic acids as potential inhibitors of factor XIa., Lazarova TI, Jin L, Rynkiewicz M, Gorga JC, Bibbins F, Meyers HV, Babine R, Strickler J, Bioorg Med Chem Lett. 2006 Oct 1;16(19):5022-7. Epub 2006 Jul 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16876411 16876411]
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*[[Factor XIa 3D structures|Factor XIa 3D structures]]
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[[Category: Coagulation factor XIa]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Babine, R.]]
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[[Category: Babine R]]
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[[Category: Bibbins, F.]]
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[[Category: Bibbins F]]
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[[Category: Gorga, J.C.]]
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[[Category: Gorga JC]]
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[[Category: Jin, L.]]
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[[Category: Jin L]]
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[[Category: Lazarova, T.I.]]
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[[Category: Lazarova TI]]
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[[Category: Meyers, H.V.]]
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[[Category: Meyers HV]]
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[[Category: Rynkiewicz, M.]]
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[[Category: Rynkiewicz M]]
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[[Category: Strickler, J.]]
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[[Category: Strickler J]]
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[[Category: 368]]
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[[Category: GOL]]
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[[Category: SO4]]
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[[Category: boron]]
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[[Category: covalent inhibitor]]
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[[Category: serine protease]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:36:26 2007''
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Current revision

Factor XI catalytic domain complexed with 2-guanidino-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl nicotinate

PDB ID 1zlr

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