1IL5

STRUCTURE OF RICIN A CHAIN BOUND WITH INHIBITOR 2,5-DIAMINO-4,6-DIHYDROXYPYRIMIDINE (DDP)

1IL5 の概要

• エントリーDOI: 10.2210/pdb1il5/pdb
• 関連するPDBエントリー: 1BR5 1BR6 1FMP 1IL3 1IL4 1IL9 1RTC
• 分子名称: RICIN A CHAIN, 2,4-DIAMINO-4,6-DIHYDROXYPYRIMIDINE (3 entities in total)
• 機能のキーワード: structure-based design, toxin-inhibitor complex, glycosidase, hydrolase, ribosome-inhibiting protein
• 由来する生物種: Ricinus communis (castor bean)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60015.63

構造登録者

Miller, D.J.,Ravikumar, K.,Shen, H.,Suh, J.-K.,Kerwin, S.M.,Robertus, J.D. (登録日: 2001-05-07, 公開日: 2002-01-16, 最終更新日: 2024-03-13)

主引用文献

Miller, D.J.,Ravikumar, K.,Shen, H.,Suh, J.K.,Kerwin, S.M.,Robertus, J.D.
Structure-based design and characterization of novel platforms for ricin and shiga toxin inhibition.
J.Med.Chem., 45:90-98, 2002

PubMed Abstract: Ribosome inhibiting proteins, RIPs, are a widespread family of toxic enzymes. Ricin is a plant toxin used as a poison and biological warfare agent; shiga toxin is a homologue expressed by pathogenic strains of E. coli. There is interest in creating effective antidote inhibitors to this class of enzymes. RIPs act by binding and hydrolyzing a specific adenine base from rRNA. Previous virtual screens revealed that pterins could bind in the specificity pocket of ricin and inhibit the enzyme. In this paper we explore a range of compounds that could serve as better platforms for inhibitor design. This establishes the importance of key hydrogen bond donors and acceptors for active-site complementarity. 8-Methyl-9-oxoguanine is a soluble compound that has the best inhibitory properties of any platform tested. The X-ray structure of this complex revealed that the inhibitor binds in an unexpected way that provides insight for future design. Several inhibitors of ricin were also shown to be inhibitors of shiga toxin, suggesting this program has the potential to develop effective antidotes to an important form of food poisoning.

PubMed: 11754581
DOI: 10.1021/jm010186s

実験手法

X-RAY DIFFRACTION (2.8 Å)