6twc

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==Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Double Bridged Peptide F21==
==Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Double Bridged Peptide F21==
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<StructureSection load='6twc' size='340' side='right'caption='[[6twc]]' scene=''>
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<StructureSection load='6twc' size='340' side='right'caption='[[6twc]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TWC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TWC FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6twc]] is a 3 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=6TWC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TWC FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6twc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6twc OCA], [http://pdbe.org/6twc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6twc RCSB], [http://www.ebi.ac.uk/pdbsum/6twc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6twc ProSAT]</span></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACN:ACETONE'>ACN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LTN:L-TRYPTOPHANAMIDE'>LTN</scene></td></tr>
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<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>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6twc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6twc OCA], [http://pdbe.org/6twc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6twc RCSB], [http://www.ebi.ac.uk/pdbsum/6twc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6twc ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[[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>
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== Function ==
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[[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The oral administration of peptide drugs is hampered by their metabolic instability and limited intestinal uptake. Here, we describe a method for the generation of small target-specific peptides (less than 1,600 Da in size) that resist gastrointestinal proteases. By using phage display to screen large libraries of genetically encoded double-bridged peptides on protease-resistant fd bacteriophages, we generated a peptide inhibitor of the coagulation Factor XIa with nanomolar affinity that resisted gastrointestinal proteases in all regions of the gastrointestinal tract of mice after oral administration, enabling more than 30% of the peptide to remain intact, and small quantities of it to reach the blood circulation. We also developed a gastrointestinal-protease-resistant peptide antagonist for the interleukin-23 receptor, which has a role in the pathogenesis of Crohn's disease and ulcerative colitis. The de novo generation of targeted peptides that resist proteolytic degradation in the gastrointestinal tract should help the development of effective peptides for oral delivery.
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De novo development of proteolytically resistant therapeutic peptides for oral administration.,Kong XD, Moriya J, Carle V, Pojer F, Abriata LA, Deyle K, Heinis C Nat Biomed Eng. 2020 May;4(5):560-571. doi: 10.1038/s41551-020-0556-3. Epub 2020 , May 11. PMID:32393891<ref>PMID:32393891</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6twc" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Coagulation factor XIa]]
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Heinis C]]
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[[Category: Heinis, C]]
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[[Category: Kong XD]]
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[[Category: Kong, X D]]
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[[Category: Pojer F]]
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[[Category: Pojer, F]]
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[[Category: Blood clotting]]
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[[Category: Coagulation factor]]
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[[Category: Double bridged peptide]]
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[[Category: Inhibitor]]
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[[Category: Phage display]]
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[[Category: Protease]]

Revision as of 07:32, 27 May 2020

Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Double Bridged Peptide F21

PDB ID 6twc

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