Thermal proteome profiling reveals fructose-1,6-bisphosphate as a phosphate donor to activate phosphoglycerate mutase 1

Deep understanding of sugar metabolite-protein interactions should provide implications on sugar metabolic reprogramming in human physiopathology. Although tremendous efforts have been made for determining individual event, global profiling of such interactome remains challenging. Here we describe thermal proteome profiling of glycolytic metabolite fructose-1,6-bisphosphate (FBP)-interacting proteins. Our results reveal a chemical signaling role of FBP which acts as a phosphate donor to activate phosphoglycerate mutase 1 (PGAM1) and contribute an intrapathway feedback for glycolysis and cell proliferation. At molecular level, FBP donates either C1-O-phosphate or C6-O-phosphate to the catalytic histidine of PGAM1 to form 3-phosphate histidine (3-pHis) modification. Importantly, structure-activity relationship studies facilitate the discovery of PGAM1 orthostatic inhibitors which can potentially restrain cancer cell proliferation. Collectively we have profiled a spectrum of FBP interactome, and discovered a unique covalent signaling function of FBP that supports Warburg effect via histidine phosphorylation which inspires the development of pharmacological tools targeting sugar metabolism.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2024-10-16
DOI
https://doi.org/10.1038/s41467-024-53238-w
Citations
13
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
Field-Weighted Citation Impact
3.71

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Thermal proteome profiling reveals fructose-1,6-bisphosphate as a phosphate donor to activate phosphoglycerate mutase 1

Ning Zhou, Yuan Liu, Richard Cheng, Huixin Luo et al.
13 citations
Nature Communications
Cancer, Hypoxia, and Metabolism
3.71
article

Thermal proteome profiling reveals fructose-1,6-bisphosphate as a phosphate donor to activate phosphoglycerate mutase 1

Ning Zhou, Yuan Liu, Richard Cheng, Huixin Luo, Zhenghui Chen, Ming Xu, Houhua Li, Xia Wu, Yiqun Geng, Anhui Wang, Jing Li, Wei Chen, Bowen Chen, Yanshen Guo, Yafei Cao, Yuanpei Li, Zhang Yan-ling, Rui Xue, Zihua Liu, Li Tian, Xiaohui Zhao
article en
13 citations

Abstract

Deep understanding of sugar metabolite-protein interactions should provide implications on sugar metabolic reprogramming in human physiopathology. Although tremendous efforts have been made for determining individual event, global profiling of such interactome remains challenging. Here we describe thermal proteome profiling of glycolytic metabolite fructose-1,6-bisphosphate (FBP)-interacting proteins. Our results reveal a chemical signaling role of FBP which acts as a phosphate donor to activate phosphoglycerate mutase 1 (PGAM1) and contribute an intrapathway feedback for glycolysis and cell proliferation. At molecular level, FBP donates either C1-O-phosphate or C6-O-phosphate to the catalytic histidine of PGAM1 to form 3-phosphate histidine (3-pHis) modification. Importantly, structure-activity relationship studies facilitate the discovery of PGAM1 orthostatic inhibitors which can potentially restrain cancer cell proliferation. Collectively we have profiled a spectrum of FBP interactome, and discovered a unique covalent signaling function of FBP that supports Warburg effect via histidine phosphorylation which inspires the development of pharmacological tools targeting sugar metabolism.

Nature CommunicationsVol. 15(1)
Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Beijing National Laboratory for Molecular Sciences (CN), Jinhua Academy of Agricultural Sciences (CN), Peking University Third Hospital (CN), Zhejiang University (CN), Capital Normal University (CN)
National Natural Science Foundation of China, Chinese Academy of Medical Sciences, Peking Union Medical College, Bijzonder Onderzoeksfonds UGent
Openalex Percentile: Top 6%
Cancer, Hypoxia, and Metabolism
3.71
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.