4ZHL

The crystal structure of mupain-1-IG in complex with murinised human uPA at pH7.4

4ZHL の概要

• エントリーDOI: 10.2210/pdb4zhl/pdb
• 関連するPDBエントリー: 4ZHM
• 分子名称: Urokinase-type plasminogen activator, mupain-1-IG (3 entities in total)
• 機能のキーワード: peptides inhibitor, upa, serine protease, 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: 29003.06

構造登録者

Jiang, L.,Andreasen, P.A.,Huang, M. (登録日: 2015-04-25, 公開日: 2015-09-16, 最終更新日: 2024-10-16)

主引用文献

Srensen, H.P.,Xu, P.,Jiang, L.,Kromann-Hansen, T.,Jensen, K.J.,Huang, M.,Andreasen, P.A.
Selection of High-Affinity Peptidic Serine Protease Inhibitors with Increased Binding Entropy from a Back-Flip Library of Peptide-Protease Fusions.
J.Mol.Biol., 427:3110-3122, 2015

PubMed Abstract: We have developed a new concept for designing peptidic protein modulators, by recombinantly fusing the peptidic modulator, with randomized residues, directly to the target protein via a linker and screening for internal modulation of the activity of the protein. We tested the feasibility of the concept by fusing a 10-residue-long, disulfide-bond-constrained inhibitory peptide, randomized in selected positions, to the catalytic domain of the serine protease murine urokinase-type plasminogen activator. High-affinity inhibitory peptide variants were identified as those that conferred to the fusion protease the lowest activity for substrate hydrolysis. The usefulness of the strategy was demonstrated by the selection of peptidic inhibitors of murine urokinase-type plasminogen activator with a low nanomolar affinity. The high affinity could not have been predicted by rational considerations, as the high affinity was associated with a loss of polar interactions and an increased binding entropy.

PubMed: 26281711
DOI: 10.1016/j.jmb.2015.08.005

実験手法

X-RAY DIFFRACTION (2.06 Å)