6l63

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==Human Coagulation Factor XIIa (FXIIa) bound with the macrocyclic peptide F3 containing two (1S,2S)-2-ACHC residues==
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<StructureSection load='6l63' size='340' side='right'caption='[[6l63]]' scene=''>
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<StructureSection load='6l63' size='340' side='right'caption='[[6l63]], [[Resolution|resolution]] 3.00&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= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6l63]] is a 4 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=6L63 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L63 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=6l63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l63 OCA], [http://pdbe.org/6l63 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l63 RCSB], [http://www.ebi.ac.uk/pdbsum/6l63 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l63 ProSAT]</span></td></tr>
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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]] 3&#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=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=E6F:(1~{S},2~{S})-2-azanylcyclohexane-1-carboxylic+acid'>E6F</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</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=6l63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l63 OCA], [https://pdbe.org/6l63 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l63 RCSB], [https://www.ebi.ac.uk/pdbsum/6l63 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l63 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FA12_HUMAN FA12_HUMAN] Congenital factor XII deficiency;Hereditary angioedema type 3. Defects in F12 are the cause of factor XII deficiency (FA12D) [MIM:[https://omim.org/entry/234000 234000]; also known as Hageman factor deficiency. This trait is an asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. F12 deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection).<ref>PMID:8528215</ref> <ref>PMID:2882793</ref> <ref>PMID:2510163</ref> <ref>PMID:8049433</ref> <ref>PMID:9354665</ref> <ref>PMID:10361128</ref> <ref>PMID:11776307</ref> <ref>PMID:15205584</ref> <ref>PMID:15617741</ref> Defects in F12 are the cause of hereditary angioedema type 3 (HAE3) [MIM:[https://omim.org/entry/610618 610618]; also known as estrogen-related HAE or hereditary angioneurotic edema with normal C1 inhibitor concentration and function. HAE is characterized by episodic local subcutaneous edema, and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE3 occurs exclusively in women and is precipitated or worsened by high estrogen levels (e.g. during pregnancy or treatment with oral contraceptives). It differs from HAE types 1 and 2 in that both concentration and function of C1 inhibitor are normal.<ref>PMID:16638441</ref> <ref>PMID:17186468</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/FA12_HUMAN FA12_HUMAN] Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa.<ref>PMID:21304106</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Peptides that contain beta-amino acids display stable secondary structures, such as helices and sheets, and are often referred to as foldamers. Cyclic beta(2,3)-amino acids (cbetaAAs), such as 2-aminocyclohexanecarboxylic acid (2-ACHC), are strong helix/turn inducers due to their restricted conformations. Here we report the ribosomal synthesis of foldamer peptides that contain multiple, up to ten, consecutive cbetaAAs via genetic code reprogramming. We also report the de novo discovery of macrocyclic cbetaAA-containing peptides capable of binding to a protein target. As a demonstration, potent binders with low-to-subnanomolar K(D) values were identified for human factor XIIa (hFXIIa) and interferon-gamma receptor 1, from a library of their 10(12) members. One of the anti-hFXIIa macrocyclic peptides that exhibited a high inhibitory activity and serum stability was co-crystallized with hFXIIa. The X-ray structure revealed that it adopts an antiparallel beta-sheet structure induced by a (1S,2S)-2-ACHC residue via the formation of two gamma-turns. This work demonstrates the potential of this platform to explore the previously inaccessible sequence space of cbetaAA-containing peptides.
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Ribosomal synthesis and de novo discovery of bioactive foldamer peptides containing cyclic beta-amino acids.,Katoh T, Sengoku T, Hirata K, Ogata K, Suga H Nat Chem. 2020 Nov;12(11):1081-1088. doi: 10.1038/s41557-020-0525-1. Epub 2020 , Aug 24. PMID:32839601<ref>PMID:32839601</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 6l63" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[3D structures of FXII|3D structures of FXII]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Synthetic construct]]
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[[Category: Hirata K]]
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[[Category: Katoh T]]
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[[Category: Ogata K]]
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[[Category: Sengoku T]]
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[[Category: Suga H]]

Revision as of 10:29, 15 November 2023

Human Coagulation Factor XIIa (FXIIa) bound with the macrocyclic peptide F3 containing two (1S,2S)-2-ACHC residues

PDB ID 6l63

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