6AOD

FXIa antibody complex

6AOD の概要

• エントリーDOI: 10.2210/pdb6aod/pdb
• 分子名称: FXIa Antibody FAB Light Chain, FXIa Antibody FAB Heavy Chain, Coagulation factor XI, ... (8 entities in total)
• 機能のキーワード: fxia antibody fab, blood clotting, blood clotting-immune system complex, blood clotting/immune system
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Secreted: P03951
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 77676.81

構造登録者

Lolicato, M.,Minor, D.L. (登録日: 2017-08-15, 公開日: 2018-03-14, 最終更新日: 2024-11-13)

主引用文献

Ely, L.K.,Lolicato, M.,David, T.,Lowe, K.,Kim, Y.C.,Samuel, D.,Bessette, P.,Garcia, J.L.,Mikita, T.,Minor, D.L.,Coughlin, S.R.
Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa Monoclonal Antibody and a Reversal Agent.
Structure, 26:187-198.e4, 2018

PubMed Abstract: Coagulation factor XIa is a candidate target for anticoagulants that better separate antithrombotic efficacy from bleeding risk. We report a co-crystal structure of the FXIa protease domain with DEF, a human monoclonal antibody that blocks FXIa function and prevents thrombosis in animal models without detectable increased bleeding. The light chain of DEF occludes the FXIa S1 subsite and active site, while the heavy chain provides electrostatic interactions with the surface of FXIa. The structure accounts for the specificity of DEF for FXIa over its zymogen and related proteases, its active-site-dependent binding, and its ability to inhibit substrate cleavage. The inactive FXIa protease domain used to obtain the DEF-FXIa crystal structure reversed anticoagulant activity of DEF in plasma and in vivo and the activity of a small-molecule FXIa active-site inhibitor in vitro. DEF and this reversal agent for FXIa active-site inhibitors may help support clinical development of FXIa-targeting anticoagulants.

PubMed: 29336885
DOI: 10.1016/j.str.2017.12.010

実験手法

X-RAY DIFFRACTION (1.8 Å)