6l63
From Proteopedia
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== Function == | == Function == | ||
[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> | [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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| - | == Publication Abstract from PubMed == | ||
| - | 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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| - | <div class="pdbe-citations 6l63" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Human Coagulation Factor XIIa (FXIIa) bound with the macrocyclic peptide F3 containing two (1S,2S)-2-ACHC residues
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