3BN9

Crystal Structure of MT-SP1 in complex with Fab Inhibitor E2

3BN9 の概要

• エントリーDOI: 10.2210/pdb3bn9/pdb
• 関連するPDBエントリー: 3BN5
• 分子名称: Membrane-type serine protease 1, E2 Fab Light Chain, E2 Fab Heavy Chain, ... (6 entities in total)
• 機能のキーワード: antibody-protease complex, protein-protein complex, enzyme-inhibitor complex, disease mutation, glycoprotein, hydrolase, membrane, polymorphism, serine protease, signal-anchor, transmembrane
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane ; Single-pass type II membrane protein : Q9Y5Y6
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 154648.53

構造登録者

Farady, C.J.,Schneider, E.L.,Egea, P.F.,Goetz, D.H.,Craik, C.S. (登録日: 2007-12-13, 公開日: 2008-09-09, 最終更新日: 2024-11-06)

主引用文献

Farady, C.J.,Egea, P.F.,Schneider, E.L.,Darragh, M.R.,Craik, C.S.
Structure of an Fab-protease complex reveals a highly specific non-canonical mechanism of inhibition
J.Mol.Biol., 380:351-360, 2008

PubMed Abstract: The vast majority of protein protease inhibitors bind their targets in a substrate-like manner. This is a robust and efficient mechanism of inhibition but, due to the highly conserved architecture of protease active sites, these inhibitors often exhibit promiscuity. Inhibitors that show strict specificity for one protease usually achieve this selectivity by combining substrate-like binding in the active site with exosite binding on the protease surface. The development of new, specific inhibitors can be aided greatly by binding to non-conserved regions of proteases if potency can be maintained. Due to their ability to bind specifically to nearly any antigen, antibodies provide an excellent scaffold for creating inhibitors targeted to a single member of a family of highly homologous enzymes. The 2.2 A resolution crystal structure of an Fab antibody inhibitor in complex with the serine protease membrane-type serine protease 1 (MT-SP1/matriptase) reveals the molecular basis of its picomolar potency and specificity. The inhibitor has a distinct mechanism of inhibition; it gains potency and specificity through interactions with the protease surface loops, and inhibits by binding in the active site in a catalytically non-competent manner. In contrast to most naturally occurring protease inhibitors, which have diverse structures but converge to a similar inhibitory archetype, antibody inhibitors provide an opportunity to develop divergent mechanisms of inhibition from a single scaffold.

PubMed: 18514224
DOI: 10.1016/j.jmb.2008.05.009

実験手法

X-RAY DIFFRACTION (2.173 Å)