3BG8

Crystal structure of Factor XIa in complex with Clavatadine A

3BG8 の概要

• エントリーDOI: 10.2210/pdb3bg8/pdb
• 分子名称: Coagulation factor XIa light chain, N-(4-carbamimidamidobutyl)ethanamide, BENZAMIDINE, ... (5 entities in total)
• 機能のキーワード: protease inhibitor, factor xia inhibitor complex, covalent inhibitor, alternative splicing, blood coagulation, disease mutation, glycoprotein, heparin-binding, hydrolase, polymorphism, secreted, serine protease
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted: P03951
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27643.22

構造登録者

Xue, Y.,Oster, L. (登録日: 2007-11-26, 公開日: 2008-12-09, 最終更新日: 2024-10-09)

主引用文献

Buchanan, M.S.,Carroll, A.R.,Wessling, D.,Jobling, M.,Avery, V.M.,Davis, R.A.,Feng, Y.,Xue, Y.,Oster, L.,Fex, T.,Deinum, J.,Hooper, J.N.,Quinn, R.J.
Clavatadine A, a natural product with selective recognition and irreversible inhibition of factor XIa.
J.Med.Chem., 51:3583-3587, 2008

PubMed Abstract: Bioassay-guided fractionation of a CH2Cl2/MeOH extract of the sponge Suberea clavata using the serine protease factor XIa to detect antithrombotic activity led to the isolation of the new marine natural products, clavatadines A and B. Clavatadines A and B inhibited factor XIa with IC50's of 1.3 and 27 microM, respectively. A crystal structure of protein-inhibitor (clavatadine A) complex was obtained and revealed interesting selective binding and irreversible inhibition of factor XIa. The cocrystal structure provides guidance for the design and synthesis of future factor XIa inhibitors as antithrombotic agents.

PubMed: 18510371
DOI: 10.1021/jm800314b

実験手法

X-RAY DIFFRACTION (1.6 Å)