7Y02

Crystal structure of Ricin A chain bound with (S)-2-(2-amino-4-oxo-3,4-dihydropteridine-7-carboxamido)-3-(4-fluorophenyl)propanoic acid

7Y02 の概要

• エントリーDOI: 10.2210/pdb7y02/pdb
• 関連するPDBエントリー: 7XZS 7XZT 7XZU 7XZW
• 分子名称: Ricin A chain, (2S)-2-[(2-azanyl-4-oxidanylidene-3H-pteridin-7-yl)carbonylamino]-3-(4-fluorophenyl)propanoic acid, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase inhibitor, hydrolase
• 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: 31833.56

構造登録者

Goto, M.,Higashi, S.,Ohba, T.,Kawata, R.,Nagatsu, K.,Suzuki, S.,Saito, R. (登録日: 2022-06-03, 公開日: 2022-12-21, 最終更新日: 2023-11-29)

主引用文献

Goto, M.,Higashi, S.,Ohba, T.,Kawata, R.,Nagatsu, K.,Suzuki, S.,Anslyn, E.V.,Saito, R.
Conformational change in ricin toxin A-Chain: A critical factor for inhibitor binding to the secondary pocket.
Biochem.Biophys.Res.Commun., 627:1-4, 2022

PubMed Abstract: Ricin toxin A-chain (RTA), a toxic protein from Ricinus communis, inactivates ribosomes to induce toxicity. The active site of RTA consists of two binding pockets. Many studies have focused on developing RTA inhibitors that can simultaneously bind to these critical pockets; however, almost all the inhibitors developed so far interact with only one pocket. In the present study, we discovered that pterin-7-carboxamides with aromatic l-amino acid pendants interacted with the active site of the enzyme in a 2-to-1 mode, where one inhibitor molecule bound to the primary pocket and the second one entered the secondary pocket in the active site of RTA. X-ray crystallographic analysis of inhibitor/RTA complexes revealed that the conformational changes of Tyr80 and Asn122 in RTA were critical for triggering the entry of inhibitor molecules into the secondary pocket of the RTA active site.

PubMed: 35998389
DOI: 10.1016/j.bbrc.2022.08.008

実験手法

X-RAY DIFFRACTION (1.6 Å)