3QN7

Potent and selective bicyclic peptide inhibitor (UK18) of human urokinase-type plasminogen activator(uPA)

3QN7 の概要

• エントリーDOI: 10.2210/pdb3qn7/pdb
• 関連するPDBエントリー: 1LMW 2NWN
• 分子名称: Urokinase-type plasminogen activator, Bicyclic peptide inhibitor, 1,3,5-tris(bromomethyl)benzene, ... (4 entities in total)
• 機能のキーワード: bicyclic peptide inhibitor, chymotrypsin fold, serine protease, urokinase receptor (upar), extracellular, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P00749
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30592.25

構造登録者

Angelini, A.,Cendron, L.,Touati, J.,Winter, G.,Zanotti, G.,Heinis, C. (登録日: 2011-02-08, 公開日: 2012-02-15, 最終更新日: 2024-11-13)

主引用文献

Angelini, A.,Cendron, L.,Chen, S.,Touati, J.,Winter, G.,Zanotti, G.,Heinis, C.
Bicyclic peptide inhibitor reveals large contact interface with a protease target
Acs Chem.Biol., 7:817-821, 2012

PubMed Abstract: From a large combinatorial library of chemically constrained bicyclic peptides we isolated a selective and potent (K(i) = 53 nM) inhibitor of human urokinase-type plasminogen activator (uPA) and crystallized the complex. This revealed an extended structure of the peptide with both peptide loops engaging the target to form a large interaction surface of 701 Å(2) with multiple hydrogen bonds and complementary charge interactions, explaining the high affinity and specificity of the inhibitor. The interface resembles that between two proteins and suggests that these constrained peptides have the potential to act as small protein mimics.

PubMed: 22304751
DOI: 10.1021/cb200478t

実験手法

X-RAY DIFFRACTION (1.9 Å)