9j7u

H176A mutant of human G6PC1 in complex with G6P

spinqualitylabelsall models 9j7u, resolution 3.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9j7u is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.14Å Ligands: BG6, POV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease G6PC1_HUMAN Glycogen storage disease due to glucose-6-phosphatase deficiency type Ia. The disease is caused by variants affecting the gene represented in this entry. Function G6PC1_HUMAN Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. Forms with the glucose-6-phosphate transporter (SLC37A4/G6PT) the complex responsible for glucose production in the terminal step of glycogenolysis and gluconeogenesis. Hence, it is the key enzyme in homeostatic regulation of blood glucose levels. Publication Abstract from PubMed The glucose-6-phosphatase (G6Pase) is an integral membrane protein that catalyzes the hydrolysis of glucose-6-phosphate (G6P) in the endoplasmic reticulum lumen and plays a vital role in glucose homeostasis. Dysregulation or genetic mutations of G6Pase are associated with diabetes and glycogen storage disease 1a (GSD-1a). Studies have characterized the biophysical and biochemical properties of G6Pase; however, the structure and substrate recognition mechanism of G6Pase remain unclear. Here, we present two cryo-EM structures of the 40-kDa human G6Pase: a wild-type apo form and a mutant G6Pase-H176A with G6P bound, elucidating the structural basis for substrate recognition and hydrolysis. G6Pase comprises nine transmembrane helices and possesses a large catalytic pocket facing the lumen. Unexpectedly, G6P binding induces substantial conformational rearrangements in the catalytic pocket, which facilitate the binding of the sugar moiety. In conjunction with functional analyses, this study provides critical insights into the structure, substrate recognition, catalytic mechanism, and pathology of G6Pase. Structural insights into glucose-6-phosphate recognition and hydrolysis by human G6PC1.,Xia Z, Liu C, Wu D, Chen H, Zhao J, Jiang D Proc Natl Acad Sci U S A. 2025 Jan 28;122(4):e2418316122. doi: , 10.1073/pnas.2418316122. Epub 2025 Jan 23. PMID:39847333 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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