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Crystal structure of ricin toxin A chain complexed with a highly potent pterin-based small-molecular inhibitor. 2023

Masaru Goto, and Natsumi Sakamoto, and Shoko Higashi, and Rena Kawata, and Kazuki Nagatsu, and Ryota Saito
Department of Molecular Bioscience, Toho University, Japan.

Ricin toxin A chain (RTA), from Ricinus communis, is a deadly protein that inactivates ribosomes by degrading an adenine residue at position 4324 in 28S rRNA. Recently, we have demonstrated that pterin-7-carboxamides with peptide pendants were potent RTA inhibitors. Among these, N-(pterin-7-carbonyl)glycyl-L-tyrosine (7PCGY) is the most potent RTA inhibitor as a small organic molecule. However, despite this fascinating inhibitory activity, the mode of interaction of 7PCGY with RTA remains elusive. This study aimed to elucidate the factors responsible for the high RTA inhibitory activity of 7PCGY based on X-ray crystallographic analysis. Herein, we report the successfully resolved X-ray crystal structure of 7PCGY/RTA complexes, revealing that the interaction between the phenolic hydroxy group in 7PCGY and Asn78 of RTA through a hydrogen bonding and the conformational change of Tyr80 and Asn122 are responsible for the high RTA inhibitory activity of 7PCGY.

UI MeSH Term Description Entries
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011622 Pterins Compounds based on 2-amino-4-hydroxypteridine. Pterin
D012276 Ricin A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. Castor Bean Lectin,Lectin, Castor Bean,Lectin, Ricinus,Ricin Toxin,RCA 60,RCA60,Ricin A Chain,Ricin B Chain,Ricin D,Ricin I,Ricinus Toxin,A Chain, Ricin,B Chain, Ricin,Ricinus Lectin,Toxin, Ricin,Toxin, Ricinus
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies

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