3WC5

Carboxypeptidase B in complex with DD9

3WC5 の概要

• エントリーDOI: 10.2210/pdb3wc5/pdb
• 関連するPDBエントリー: 3WAB 3WC6 3WC7
• 分子名称: Carboxypeptidase B, ZINC ION, (2R)-7-amino-2-(selanylmethyl)heptanoic acid, ... (5 entities in total)
• 機能のキーワード: selen, organoselenium, selenium, selenol, cpb inhibitor, second zinc, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Sus scrofa (Pig)
• 細胞内の位置: Secreted : P09955
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35311.26

構造登録者

Yoshimoto, N.,Itoh, T.,Inaba, Y.,Yamamoto, K. (登録日: 2013-05-24, 公開日: 2013-10-02, 最終更新日: 2024-11-06)

主引用文献

Yoshimoto, N.,Itoh, T.,Inaba, Y.,Ishii, H.,Yamamoto, K.
Structural basis for inhibition of carboxypeptidase B by selenium-containing inhibitor: selenium coordinates to zinc in enzyme.
J.Med.Chem., 56:7527-7535, 2013

PubMed Abstract: Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) is a zinc-containing carboxypeptidase and significantly inhibits fibrinolysis. TAFIa inhibitors are thus expected to act as profibrinolytic agents. We recently reported the design and synthesis of selenium-containing inhibitors of TAFIa and their inhibitory activity. Here we report the crystal structures of potent selenium-, sulfur-, and phosphinic acid-containing inhibitors bound to porcine pancreatic carboxypeptidase B (ppCPB). ppCPB is a TAFIa homologue and is surrogate TAFIa for crystallographic analysis. Crystal structures of ppCPB complexed with selenium compound 1a, its sulfur analogue 2, and phosphinic acid derivative EF6265 were determined at 1.70, 2.15, and 1.90 Å resolution, respectively. Each inhibitor binds to the active site of ppCPB in a similar manner to that observed for previously reported inhibitors. Thus, in complexes, selenium, sulfur, and phosphinic acid oxygen coordinate to zinc in ppCPB. This is the first observation and report of selenium coordinating to zinc in CPB.

PubMed: 24010887
DOI: 10.1021/jm400816v

実験手法

X-RAY DIFFRACTION (1.7 Å)