View source for 1zmj


==Crystal Structure of the Catalytic Domain of Factor XI in complex with 4-(guanidinomethyl)-phenylboronic acid==
<StructureSection load='1zmj' size='340' side='right' caption='[[1zmj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zmj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZMJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HDB:(R)-1-(4-(4-(HYDROXYMETHYL)-1,3,2-DIOXABOROLAN-2-YL)BENZYL)GUANIDINE'>HDB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1zmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zmj OCA], [http://pdbe.org/1zmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zmj RCSB], [http://www.ebi.ac.uk/pdbsum/1zmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zmj ProSAT]</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. 
== 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/zm/1zmj_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1zmj ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1zmj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Coagulation factor XIa]]
[[Category: Human]]
[[Category: Babine, R E]]
[[Category: Bibbins, F]]
[[Category: Gorga, J C]]
[[Category: Jin, L]]
[[Category: Lazarova, T I]]
[[Category: Meyers, H V]]
[[Category: Rynkiewicz, M J]]
[[Category: Strickler, J E]]
[[Category: Fxi]]
[[Category: Hydrolase]]
[[Category: Inhibitor]]