Department of Molecular Bioscience, Toho University, Japan.
Department of Chemistry, Toho University, Japan.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2219038. doi: 10.1080/14756366.2023.2219038.
Ricin toxin A chain (RTA), from , 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, -(pterin-7-carbonyl)glycyl-L-tyrosine () is the most potent RTA inhibitor as a small organic molecule. However, despite this fascinating inhibitory activity, the mode of interaction of with RTA remains elusive. This study aimed to elucidate the factors responsible for the high RTA inhibitory activity of based on X-ray crystallographic analysis. Herein, we report the successfully resolved X-ray crystal structure of /RTA complexes, revealing that the interaction between the phenolic hydroxy group in 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 .
蓖麻毒素 A 链（RTA）来源于 ，是一种致命的蛋白质，通过在 28S rRNA 的位置 4324 处降解腺嘌呤残基来使核糖体失活。最近，我们已经证明具有肽侧链的蝶呤-7-甲酰胺是有效的 RTA 抑制剂。在这些抑制剂中，-(蝶呤-7-羰基)甘氨酰-L-酪氨酸（ ）作为小分子有机化合物是最有效的 RTA 抑制剂。然而，尽管具有这种迷人的抑制活性，但 与 RTA 的相互作用模式仍然难以捉摸。本研究旨在通过 X 射线晶体学分析阐明 对 RTA 具有高抑制活性的原因。在此，我们报告了 /RTA 复合物的成功解析的 X 射线晶体结构，揭示了 中酚羟基与 RTA 的 Asn78 之间通过氢键相互作用以及 Tyr80 和 Asn122 的构象变化是 对 RTA 具有高抑制活性的原因。
Zotero 插件
