9X4F

Crystal structure of tetrameric alpha-enolase with asymmetric flexible active sites

Summary for 9X4F

• Entry DOI: 10.2210/pdb9x4f/pdb
• Descriptor: Alpha-enolase, MAGNESIUM ION (3 entities in total)
• Functional Keywords: conformational change, asymmetric, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 195397.08

Authors

Yan, X.,Biao, Y. (deposition date: 2025-10-10, release date: 2026-07-15)

Primary citation

Xia, Y.,Xia, M.,Dai, Z.,Fang, P.,Fang, P.,Wang, J.,Zhu, D.,Luo, C.,Xu, H.,Yu, B.
Natural Glycoside OSW-1 Targets Glycolytic Enzyme Enolase 1 to Reprogram Tumor Metabolism via Glycolytic Blockade.
Acs Chem.Biol., 21:790-800, 2026

PubMed Abstract: OSW-1, a steroidal disaccharide isolated from the bulbs of , has been extensively studied for its extremely potent cytotoxicity against the National Cancer Institute's 60 cancer cell lines with an average IC of 0.78 nM, while exhibiting selectivity toward normal cells. Although OSBP and ORP4L have been identified as its binding targets, their known functions appear insufficient to account for the compound's exceptional potency, suggesting the involvement of additional mechanisms and targets. Therefore, elucidating novel target proteins associated with its activity is essential for the further development of this molecule. Here, we disclose that OSW-1 can block the glycolytic pathway and trigger compensatory mitochondrial oxidative phosphorylation. This previously uncharacterized mechanism is relevant to the key rate-limiting enzyme, enolase 1 (ENO1), which shows subnanomolar affinity with OSW-1. Our study repurposes OSW-1 to be a small-molecule probe to investigate the function of ENO1 and a promising candidate for metabolism-targeted anticancer therapy.

PubMed: 41855411
DOI: 10.1021/acschembio.6c00022

Experimental method

X-RAY DIFFRACTION (2.7 Å)