3EJ5

complex of Ricin A chain and pyrimidine-based inhibitor

3EJ5 の概要

• エントリーDOI: 10.2210/pdb3ej5/pdb
• 分子名称: Ricin A chain, 4-[3-(2-amino-4-hydroxy-6-oxo-1,6-dihydropyrimidin-5-yl)propyl]benzoic acid (3 entities in total)
• 機能のキーワード: protein inhibitor complex, glycoprotein, hydrolase, lectin, nucleotide-binding, plant defense, protein synthesis inhibitor, toxin
• 由来する生物種: Ricinus communis (Castor bean)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29051.70

構造登録者

Bai, Y.,Monzingo, A.F.,Robertus, J.D. (登録日: 2008-09-17, 公開日: 2009-04-07, 最終更新日: 2023-08-30)

主引用文献

Bai, Y.,Monzingo, A.F.,Robertus, J.D.
The X-ray structure of ricin A chain with a novel inhibitor
Arch.Biochem.Biophys., 483:23-28, 2009

PubMed Abstract: Ricin is a potent heterodimeric cytotoxin; the B chain binds eucaryotic cell surfaces aiding uptake and the A chain, RTA, reaches the cytoplasm where it enzymatically depurinates a key ribosomal adenine, inhibiting protein synthesis. Ricin is known to be an agent in bioterrorist repertoires and there is great interest in finding, or creating, efficacious inhibitors of the toxin as potential antidotes. We have previously identified two families of bicyclic RTA inhibitors, pterins and purines. Both classes have poor solubility which impairs inhibitor development. Here we report the use of 2-amino-4,6-dihydroxy-pyrimidines as RTA inhibitors. Unlike previously observed single ring inhibitor platforms, these displace Tyr 80 and bind deep in the RTA specificity pocket. These compounds are at least 10 times more soluble than pterin-based inhibitors and appear to be useful new class of ricin inhibitors.

PubMed: 19138659
DOI: 10.1016/j.abb.2008.12.013

実験手法

X-RAY DIFFRACTION (2.5 Å)