Structural basis for substrate recognition and inhibition of human glucose-6-phosphate transporter SLC37A4. (PubMed, PLoS Biol) - Jul 29, 2026 - "Here we report cryo-electron microscopy structures of human SLC37A4 in three states: the apo form at 2.8 Å resolution, a G6P-bound state at 3.2 Å resolution and a chlorogenic acid (CHA) bound state at 3.3 Å resolution...Combined with thermostability and transport-based analyses of G6P binding and disease variants, these structures support a rocker switch mechanism in which electrostatic neutralization of the central positively charged cavity by anionic substrate drives the conformational changes underlying G6P/Pi exchange. Together, these findings define the structural basis of G6P/Pi exchange by SLC37A4, provide a molecular rationale for pathogenic mutations in glycogen storage disease type Ib, and provide a framework for targeting SLC37A4 to modulate G6P homeostasis."
Journal • Metabolic Disorders
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Hui Li; Nan Li; Wencheng Wu; Xiaomin Peng; Xuepeng Wei; Yuwen Huang; Ziqi Cheng
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