Identification and verification of methylenetetrahydrofolate dehydrogenase 1-like protein as the binding target of natural product pseudolaric acid A

IF 4.8 3区化学 Q1 CHEMISTRY, MEDICINAL

Natural Products and Bioprospecting Pub Date : 2025-04-02 DOI:10.1007/s13659-025-00502-1

Haoqi Dong, Xinni Yang, Peiying Wang, Weiya Huang, Liang Zhang, Song Song, Jiangxin Liu

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引用次数: 0

Abstract

Natural product pseudolaric acid A (PAA), the main bioactive component from Traditional Chinese Medicine Pseudolarix cortex (“tujingpi”), is a promising anticancer agent. However, its potential molecular targets are not clear and this hinders its development. In this study, chemical proteomics approaches including activity-based protein profiling (ABPP) and drug affinity responsive target stability (DARTS) technology, followed by quantitative proteomics, were combined to reveal the target of PAA. Target validation was performed by NMR techniques and surface plasmon resonance. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) was identified and further confirmed to be the target of PAA. The direct interaction and binding mode between MTHFD1L and PAA were elaborated. PAA induced the accumulation of the reactive oxygen species (ROS) which mediates the antitumor effect. Transcriptome and network pharmacology analysis reveals the effects of PAA on the gene expressions of the associated pathways. Taken together, our findings proposed a new target that could be used for structure-based rational design and modifications of PAA.

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来源期刊

Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-

CiteScore

8.30

自引率

2.10%

发文量

审稿时长

13 weeks

期刊介绍： Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects: Natural products: isolation and structure elucidation Natural products: synthesis Biological evaluation of biologically active natural products Bioorganic and medicinal chemistry Biosynthesis and microbiological transformation Fermentation and plant tissue cultures Bioprospecting of natural products from natural resources All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.