1PK0

Crystal Structure of the EF3-CaM complexed with PMEApp

1PK0 の概要

• エントリーDOI: 10.2210/pdb1pk0/pdb
• 関連するPDBエントリー: 1LVC
• 分子名称: Calmodulin-sensitive adenylate cyclase, Calmodulin, YTTERBIUM (III) ION, ... (6 entities in total)
• 機能のキーワード: edema factor, cam, prodrug complex, lyase-metal binding protein complex, lyase/metal binding protein
• 由来する生物種: Bacillus anthracis; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 227147.18

構造登録者

Shen, Y.,Tang, W.J. (登録日: 2003-06-04, 公開日: 2004-02-10, 最終更新日: 2024-04-03)

主引用文献

Shen, Y.,Zhukovskaya, N.L.,Zimmer, M.I.,Soelaiman, S.,Bergson, P.,Wang, C.R.,Gibbs, C.S.,Tang, W.J.
Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection.
Proc.Natl.Acad.Sci.USA, 101:3242-3247, 2004

PubMed Abstract: Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity. We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages. Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high affinity (K(i) = 27 nM). A crystal structure of EF-CaM-PMEApp reveals that the catalytic site of EF forms better van der Waals contacts and more hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the approximately 10,000-fold higher affinity EF-CaM has for PMEApp versus ATP. Adefovir dipivoxil is a clinically approved drug that can block the action of an anthrax toxin. It can be used to address the role of EF in anthrax pathogenesis.

PubMed: 14978283
DOI: 10.1073/pnas.0306552101

実験手法

X-RAY DIFFRACTION (3.3 Å)