7Y4K

Crystal structure of Ricin A chain bound with N2-(2-amino-4-oxo-3,4-dihydropteridine-7-carbonyl)glycyl-L-phenylalanyl-N6-((benzyloxy)carbonyl)-L-ornitine

7Y4K の概要

• エントリーDOI: 10.2210/pdb7y4k/pdb
• 分子名称: Ricin A chain, (2S)-2-[[(2S)-2-[2-[(2-azanyl-4-oxidanylidene-3H-pteridin-7-yl)carbonylamino]ethanoylamino]-3-phenyl-propanoyl]amino]-5-(phenylmethoxycarbonylamino)pentanoic acid, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase inhibitor, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 31748.59

構造登録者

Katakura, S.,Goto, M.,Ohba, T.,Kawata, R.,Nagatsu, K.,Higashi, S.,Matsumoto, K.,Kurisu, K.,Ohtsuka, K.,Saito, R. (登録日: 2022-06-15, 公開日: 2022-11-16, 最終更新日: 2023-11-29)

主引用文献

Saito, R.,Goto, M.,Katakura, S.,Ohba, T.,Kawata, R.,Nagatsu, K.,Higashi, S.,Kurisu, K.,Matsumoto, K.,Ohtsuka, K.
Pterin-based small molecule inhibitor capable of binding to the secondary pocket in the active site of ricin-toxin A chain.
Plos One, 17:e0277770-e0277770, 2022

PubMed Abstract: The Ricin toxin A chain (RTA), which depurinates an adenine base at a specific region of the ribosome leading to death, has two adjacent specificity pockets in its active site. Based on this structural information, many attempts have been made to develop small-molecule RTA inhibitors that simultaneously block the two pockets. However, no attempt has been successful. In the present study, we synthesized pterin-7-carboxamides with tripeptide pendants and found that one of them interacts with both pockets simultaneously to exhibit good RTA inhibitory activity. X-ray crystallographic analysis of the RTA crystal with the new inhibitor revealed that the conformational change of Tyr80 is an important factor that allows the inhibitors to plug the two pockets simultaneously.

PubMed: 36508422
DOI: 10.1371/journal.pone.0277770

実験手法

X-RAY DIFFRACTION (1.7 Å)