Evidence map›Paper›PMID 42744818›Full record

ArticleNature communications2026

Covalent allosteric inhibition of AARS1 lactyltransferase.

Yunyuan Huang, Siying Liu, Luyang Tian, Yang Tang, Yilin Dou, Huiling Wang, Tao Zheng, Mingyang Wang, Runhao Li, Zhi Wang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Yunyuan Huang *Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China. yunyuanhuang@ccnu.edu.cn.ORCID 0000-0003-1857-9498
Siying Liu *Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.
Luyang Tian *Department of Medical Ultrasound, Tongji University Affiliated Tenth People's Hospital, Shanghai, China.
Yang TangDepartment of Medical Ultrasound, Tongji University Affiliated Tenth People's Hospital, Shanghai, China.
Yilin DouHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.
Huiling WangNational Key Laboratory of Green Pesticide, College of Chemistry, Central China Normal University, Wuhan, China.
Tao ZhengState Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Pharmacy, Jinan University, Guangzhou, China.
Mingyang WangHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.
Runhao LiHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.
Zhi WangHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China.
Zhaocai ZhouState Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID 0000-0002-5441-3922
Xin ChenState Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Pharmacy, Jinan University, Guangzhou, China. chenxin2023@jnu.edu.cn.ORCID 0000-0003-2931-2158
Jinrong MinHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China. minjinrong@ccnu.edu.cn.ORCID 0000-0001-5210-3130

Funding

Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology) RGPIN-2021-02728National Natural Science Foundation of China (National Science Foundation of China) 32570711National Natural Science Foundation of China (National Science Foundation of China) 82404418National Natural Science Foundation of China (National Science Foundation of China) 82573770
6 · The paper itself

Abstract

Alanyl-tRNA synthetase 1 (AARS1) was recently identified as a lactyltransferase responsible for protein lactylation, a modification associated with epigenetic regulation and metabolic adaptation. Here, we report compound XY353, which covalently binds C184 of AARS1, inducing steric clashes with F175 and triggering structural rearrangements in the region that displace W176, a key residue for lactate binding. By means of a combination of a variety of biophysical and enzymatic assays with MD simulations and structural analysis, we show that XY353 and its derivative XY353-1 inhibit AARS1 by competing with lactate via the C184-F175-W176 relay, supporting a covalent allosteric mechanism of inhibition, which is further confirmed by our cellular data that XY353-1 reduces lactylation of the AARS1 substrate YAP and suppresses the proliferation of HGC-27 cells. Collectively, these findings identify a covalent allosteric mechanism for AARS1 inhibition and provide chemical tools to explore its biological functions.

Indexed as

Enzyme InhibitorsAllosteric RegulationCell Line, TumorCell ProliferationHumansMolecular Dynamics SimulationEnzyme Inhibitors

Identifiers

PMID42744818
PMCPMC13578339

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.