View source for 5eok


==Human Plasma Coagulation Factor XI in complex with peptide P39==
<StructureSection load='5eok' size='340' side='right'caption='[[5eok]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5eok]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EOK 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5eok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eok OCA], [https://pdbe.org/5eok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eok RCSB], [https://www.ebi.ac.uk/pdbsum/5eok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eok 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Factor XI (FXI) is the zymogen of factor XIa (FXIa) which cleaves factor IX in the intrinsic pathway of coagulation. FXI is known to exist as a dimer and form interactions with multiple proteins via its four apple domains in the "saucer section" of the enzyme however to date, no complex crystal structure has been described. To investigate protein interactions of FXI a large random peptide library consisting of 106-107peptides was screened for FXI binding and this identified a series of FXI binding motifs containing the signature Asp-Phe-Pro (DFP) tripeptide. Motifs containing this core tripeptide were found in diverse proteins including the known ligand high molecular weight kininogen (HK) as well as extracellular matrix proteins laminin and collagen V. To define the binding site on FXI we determined the crystal structure of FXI in complex with the HK derived peptide NPISDFPDT. This revealed the location of the DFP peptide bound to the FXI apple 2 domain and central to the interaction the DFP phenylalanine side chain inserts into a major hydrophobic pocket in the apple 2 domain and the isoleucine occupies a flanking minor pocket. Two further structures of FXI in complex with the laminin derived peptide EFPDFPand a DFP peptide from the random screen demonstrated binding in the same pocket although in a slightly different conformation, thus revealing some flexibility in the molecular interactions of the FXI apple 2 domain.

A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain.,Wong SS, Ostergaard S, Hall G, Li C, Williams PM, Stennicke H, Emsley J Blood. 2016 Mar 22. pii: blood-2015-10-676122. PMID:27006387<ref>PMID:27006387</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5eok" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Emsley J]]
[[Category: Hall G]]
[[Category: Li C]]
[[Category: Ostergaard S]]
[[Category: Stennicke H]]
[[Category: Williams PM]]
[[Category: Wong SS]]