5ZEQ

Carboxypeptidase B in complex with DD28

5ZEQ の概要

• エントリーDOI: 10.2210/pdb5zeq/pdb
• 分子名称: Carboxypeptidase B, ZINC ION, (2~{S})-2-[(6-azanyl-5-chloranyl-pyridin-3-yl)methyl]-3-selanyl-propanoic acid, ... (5 entities in total)
• 機能のキーワード: selenium, organoselenium, selenol, cpb inhibitor, selectivity, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Sus scrofa (Pig)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35426.12

構造登録者

Itoh, T.,Yoshimoto, N.,Yamamoto, K. (登録日: 2018-02-27, 公開日: 2018-06-20, 最終更新日: 2024-10-09)

主引用文献

Itoh, T.,Yoshimoto, N.,Hirano, Y.,Yamamoto, K.
Structural basis for the selective inhibition of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) by a selenium-containing inhibitor with chloro-aminopyridine as a basic group
Bioorg. Med. Chem. Lett., 28:2256-2260, 2018

PubMed Abstract: Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) is a target molecule for treating thromboembolic disorders. We previously reported that design and synthesis of compound 1 containing a selenol group and chloloaminopyridine. Compound 1 showed high inhibitory activity towards TAFIa, with a high degree of selectivity for TAFIa over carboxypeptidase N (CPN). Here we report investigation of this selectivity. To obtain co-crystal of 1/pp-CPB (a surrogate of TAFIa), we synthesized protected compound 5 as a stabilized precursor of 1. The X-ray crystal structure and docking study indicated that the Cl substituent is accommodated in the pp-CPB specific pocket whereas CPN has no identical pocket. This is important information for the design of drugs targeting TAFIa with high selectivity.

PubMed: 29859906
DOI: 10.1016/j.bmcl.2018.05.042

実験手法

X-RAY DIFFRACTION (1.9 Å)