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- PDB-9ll1: Cryo-EM structure of G6PT1 in complex with Chlorogenic acid -

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Basic information

Entry
Database: PDB / ID: 9ll1
TitleCryo-EM structure of G6PT1 in complex with Chlorogenic acid
ComponentsGlucose-6-phosphate exchanger SLC37A4
KeywordsTRANSPORT PROTEIN / protein structure / STRUCTURAL PROTEIN
Function / homology
Function and homology information


glucose-6-phosphate transmembrane transporter activity / Glycogen storage disease type Ib (SLC37A4) / glucose-6-phosphate transport / glucose 6-phosphate:phosphate antiporter activity / Gluconeogenesis / phosphate ion transmembrane transport / gluconeogenesis / glucose metabolic process / glucose homeostasis / endoplasmic reticulum membrane ...glucose-6-phosphate transmembrane transporter activity / Glycogen storage disease type Ib (SLC37A4) / glucose-6-phosphate transport / glucose 6-phosphate:phosphate antiporter activity / Gluconeogenesis / phosphate ion transmembrane transport / gluconeogenesis / glucose metabolic process / glucose homeostasis / endoplasmic reticulum membrane / endoplasmic reticulum / membrane
Similarity search - Function
Glycerate/sugar phosphate transporter, conserved site / : / glpT family of transporters signature. / Sugar phosphate transporter / Major facilitator superfamily / Major Facilitator Superfamily / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
: / Glucose-6-phosphate exchanger SLC37A4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.82 Å
AuthorsZhao, Y. / Chen, Q.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Sci Adv / Year: 2026
Title: Structural insight into the glucose-6-phosphate transport by G6PT1 and inhibition mechanism of CGA.
Authors: Qihao Chen / Pu Yuan / Renjie Li / Xiaoyue Du / Rilei Yu / Yan Zhao /
Abstract: Human glucose-6-phosphate transporter 1 (G6PT1) is responsible for transporting glucose-6-phosphate (G6P) into the endoplasmic reticulum (ER), a crucial rate-limiting step in both glycogenolysis and ...Human glucose-6-phosphate transporter 1 (G6PT1) is responsible for transporting glucose-6-phosphate (G6P) into the endoplasmic reticulum (ER), a crucial rate-limiting step in both glycogenolysis and gluconeogenesis. Complete and chronic dysfunction of G6PT1 can lead to the severe metabolic disorder GSD1b, whereas moderate and reversible inhibition contributes to diabetes treatment. We determined the structures of human G6PT1 in its apo state and in complex with the substrate G6P, cosubstrate phosphate, and the inhibitor chlorogenic acid (CGA). Captured in both lumen- and cytosol-facing conformations, these structures reveal the specific mechanism of phosphate-coupled G6P transport. In addition, the CGA-bound G6PT1 complex shows that CGA stabilizes the transporter in the cytosol-facing conformation, inhibiting it by competing with substrate binding and preventing conformational transitions, providing previously unreported insights into G6PT1 inhibition. Our findings provide a structural foundation for understanding the mechanisms of substrate recognition, transport, drug inhibition, and the pharmacology of G6PT1, paving the way to the rational design of potential therapeutic agents.
History
DepositionJan 17, 2025Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 31, 2025Provider: repository / Type: Initial release
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Glucose-6-phosphate exchanger SLC37A4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)46,7462
Polymers46,3921
Non-polymers3541
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Glucose-6-phosphate exchanger SLC37A4 / Glucose-5-phosphate transporter / Glucose-6-phosphate translocase / Solute carrier family 37 member ...Glucose-5-phosphate transporter / Glucose-6-phosphate translocase / Solute carrier family 37 member 4 / Transformation-related gene 19 protein / TRG-19


Mass: 46391.809 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC37A4, G6PT, G6PT1, PRO0685, TRG19 / Production host: Homo sapiens (human) / References: UniProt: O43826
#2: Chemical ChemComp-A1EG7 / (1S,3R,4R,5R)-3-[(E)-3-[3,4-bis(oxidanyl)phenyl]prop-2-enoyl]oxy-1,4,5-tris(oxidanyl)cyclohexane-1-carboxylic acid / CHLOROGENIC ACID


Mass: 354.309 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H18O9 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Cryo-EM structure of G6PT1 in complex with Chlorogenic acid
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 2.82 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 71558 / Symmetry type: POINT

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