Wang Jianwen, Takahashi Ikuo, Kikuzato Ko, Sakai Toshihiko, Zhu Zhangliang, Jiang Kai, Nakamura Hidemitsu, Nakano Takeshi, Tanokura Masaru, Miyakawa Takuya, Asami Tadao
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Nat Commun. 2025 Jan 2;16(1):104. doi: 10.1038/s41467-024-54801-1.
The smoke-derived butenolides, karrikins (KARs), regulate many aspects of plant growth and development. However, KARs and a plant hormone, strigolactones (SLs), have high resemblance in signal perception and transduction, making it hard to delineate KARs response due to the shortage of chemical-genetic tools. Here, we identify a triazole urea KK181N1 as an inhibitor of the KARs receptor KAI2. KK181N1 selectively depress the KAR-induced phenotypes in Arabidopsis. We further elucidate the antagonistic, KAI2 binding mechanism of KK181N1, showing that KK181N1 binds to the catalytic pockets of KAI2 in a non-covalent binding manner. Our experiments also demonstrate the binding affinity of triazole urea compounds are regulated by the structured water molecule networks. By fine-tuning this network, we successfully develop a more potent derivative of KK181N1. We anticipate that these chemicals will be applicable to the elucidation of KARs biology, especially for discriminating the molecular and physiological aspects of KARs and SL signaling.
源自烟雾的丁烯内酯类物质——独脚金内酯（KARs），调控着植物生长发育的诸多方面。然而，KARs与一种植物激素——独脚金内酯（SLs）在信号感知和转导方面高度相似，由于缺乏化学遗传学工具，难以明确KARs的反应。在此，我们鉴定出一种三唑脲类化合物KK181N1作为KARs受体KAI2的抑制剂。KK181N1能选择性地抑制拟南芥中KARs诱导的表型。我们进一步阐明了KK181N1与KAI2的拮抗结合机制，表明KK181N1以非共价结合方式与KAI2的催化口袋结合。我们的实验还证明了三唑脲类化合物的结合亲和力受结构化水分子网络调控。通过微调该网络，我们成功开发出一种活性更强的KK181N1衍生物。我们预计这些化学物质将适用于阐明KARs生物学，特别是用于区分KARs和SL信号传导的分子和生理方面。
