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July 30, 2026PLoS BiologyOpen Access

Structural basis for substrate recognition and inhibition of human glucose-6-phosphate transporter SLC37A4

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Authors

XWXuepeng WeiXPXiaomin PengYHYuwen Huang

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Overview

Researchers explore how SLC37A4 transports glucose 6 phosphate in humans, highlighting implications for glycogen storage disease type Ib.

Key Points

  • This research aims to elucidate the structural mechanisms by which SLC37A4 recognizes and transports glucose 6 phosphate (G6P).
  • Utilized cryo-electron microscopy to obtain structures of SLC37A4 in different states: apo, G6P-bound, and CHA-bound.
  • Examined the conformational changes of SLC37A4 necessary for G6P and phosphate transport.
  • Performed thermostability and transport analyses to assess G6P binding and evaluate disease variants.
  • SLC37A4 demonstrates an outward-open conformation for G6P binding and an inward-facing conformation for CHA binding.
  • The binding of CHA prevents G6P/Pi exchange by locking the transporter in place, demonstrating a rocker switch mechanism.
  • Defined structural basis for G6P/Pi exchange and offered insights into pathogenic mutations linked to glycogen storage disease type Ib.

Cite This Study

Wei et al. (2026) studied this question.

synapsesocial.com/papers/6a6af4e960e2b924d3ea0836https://doi.org/10.1371/journal.pbio.3003833
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Structures of the human glucose-6-phosphate transporter provide insights into its transport cycle and substrate recognition2026 · 3 citations
  2. 2Structures of human glucose-6-phosphate transporter reveal reciprocal antiport mechanism driving glucose-6-phosphate and inorganic phosphate exchange2025 · 4 citations
  3. 3Structural insight into the glucose-6-phosphate transport by G6PT1 and inhibition mechanism of CGA2026 · 3 citations
  4. 4Structural snapshots of the glucose-6-phosphate/phosphate exchange cycle2026
  5. 5Global Landscape of SLC37A4 Variants and Their Potential Amenability to Pharmacological Chaperone Therapy in Glycogen Storage Disease Type Ib2026