9JTO

Human glucose 6 phosphate catalytic subunit 1 (hG6PC1) bound with F6P.

Summary for 9JTO

• Entry DOI: 10.2210/pdb9jto/pdb
• EMDB information: 61814
• Descriptor: Glucose-6-phosphatase catalytic subunit 1,GSlinker-HRV3C-GFP-twin strep, O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine, 6-O-phosphono-beta-D-fructofuranose (3 entities in total)
• Functional Keywords: membrane protein, glucose metabolism, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 72929.25

Authors

Chen, Q.,Zhao, Y.,Wang, Y. (deposition date: 2024-10-05, release date: 2025-08-06)

Primary citation

Chen, Q.,Wang, Y.,Li, R.,Bai, Q.,Zhao, Y.
The induced-fit and catalytic mechanisms of human G6PC1
Cell Discov, 11:62-, 2025

PubMed Abstract: Human glucose-6-phosphatase catalytic subunit 1 (hG6PC1) is a key enzyme in glucose metabolism, governing the final common step of gluconeogenesis and glycogenolysis, and directly regulating energy homeostasis. Aberrant mutations in G6PC1 directly cause glycogen storage disease type 1a, which is characterized by chronic hypoglycemia and glycogen accumulation. Additionally, abnormal G6PC1 function leads to increased fasting blood glucose. Consequently, it is a critical target for treating glucose metabolism disorders. In this study, we determine the cryo-EM structures of G6PC1 in both the partially open and fully open states, in either the apo form or in complex with the substrates G6P or F6P and the product phosphate. These structures offer distinct insights into the mechanism of hydrolysis and induced-fit, providing a structural foundation for the diagnostic analysis of disease-causing mutations in G6PC1. Moreover, we propose a potential mechanism by which phosphatidylserine regulates G6PC1 activity, providing a novel perspective on its role and implications.

PubMed: 40664655
DOI: 10.1038/s41421-025-00814-z

Experimental method

ELECTRON MICROSCOPY (3.3 Å)