6XVD

Crystal structure of complex of urokinase and a upain-1 variant(W3F) in pH7.4 condition

6XVD の概要

• エントリーDOI: 10.2210/pdb6xvd/pdb
• 分子名称: Urokinase-type plasminogen activator, upain-1-W3F (3 entities in total)
• 機能のキーワード: upain-1-w3f, urokinase, cyclic peptide inhibitor, peptide binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29811.97

構造登録者

Xue, G.P.,Xie, X.,Zhou, Y.,Yuan, C.,Huang, M.D.,Jiang, L.G. (登録日: 2020-01-21, 公開日: 2020-02-19, 最終更新日: 2024-10-23)

主引用文献

Xue, G.,Xie, X.,Zhou, Y.,Yuan, C.,Huang, M.,Jiang, L.
Insight to the residue in P2 position prevents the peptide inhibitor from being hydrolyzed by serine proteases.
Biosci.Biotechnol.Biochem., 84:1153-1159, 2020

PubMed Abstract: Peptidic inhibitors of proteases are attracting increasing interest not only as drug candidates but also for studying the function and regulation mechanisms of these enzymes. Previously, we screened out a cyclic peptide inhibitor of human uPA [Formula: see text] and found that Ala substitution of P2 residue turns upain-1 to a substrate. To further investigate the effect of P2 residue on the peptide behavior transformation, we constructed upain-1-W3F, which has Phe replacement in the P2 position. We determined and of upain-1-W3F and found that upain-1-W3F might still exist as an inhibitor. Furthermore, the high-resolution crystal structure of upain-1-W3F·uPA reveals that upain-1-W3F indeed stays as an intact inhibitor bind to uPA. We thus propose that the P2 residue plays a nonnegligible role in the conversion of upain-1 to a substrate. These results also proposed a strategy to optimize the pharmacological properties of peptide-based drug candidates by hydrophobicity and steric hindrance. : uPA: urokinase-type plasminogen activator; SPD: serine protease domain; S1 pocket: specific substrate-binding pocket.

PubMed: 32019421
DOI: 10.1080/09168451.2020.1723405

実験手法

X-RAY DIFFRACTION (1.4 Å)