2. Academic Validation
  3. Crystal structure of ricin toxin A chain complexed with a highly potent pterin-based small-molecular inhibitor

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

  • J Enzyme Inhib Med Chem. 2023 Dec;38(1):2219038. doi: 10.1080/14756366.2023.2219038.
Masaru Goto 1,  Natsumi Sakamoto 2,  Shoko Higashi 2,  Rena Kawata 1,  Kazuki Nagatsu 1,  Ryota Saito 2 3
Affiliations

Affiliations

  • 1 Department of Molecular Bioscience, Toho University, Japan.
  • 2 Department of Chemistry, Toho University, Japan.
  • 3 Research Center for Materials with Integrated Properties, Toho University, Japan.
PMID: 37259593 DOI: 10.1080/14756366.2023.2219038
Abstract

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.

Keywords

Ricin toxin A chain; X-ray crystallography; pterin-7-carboxamide; ricin toxin A chain inhibitor.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-157328
    RTA Inhibitor