5jn5

Crystal structure of the D263Y missense variant of human PGM1

spinqualitylabelsall models 5jn5, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jn5 is a 2 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: X-ray diffraction, Resolution 1.75Å Ligands: CA, SEP, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease PGM1_HUMAN PGM-CDG;Glycogen storage disease due to phosphoglucomutase deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function PGM1_HUMAN This enzyme participates in both the breakdown and synthesis of glucose. Publication Abstract from PubMed The enzyme phosphoglucomutase 1 (PGM1) plays a central role in glucose homeostasis. Clinical studies have identified mutations in human PGM1 as the cause of PGM1 deficiency, an inherited metabolic disease. One residue, Asp263, has two known variants associated with disease: D263G and D263Y. Biochemical studies have shown that these mutants are soluble and well folded, but have significant catalytic impairment. To better understand this catalytic defect, we determined crystal structures of these two missense variants, both of which reveal a similar and indirect structural change due to the loss of a conserved salt bridge between Asp263 and Arg293. The arginine reorients into the active site, making interactions with residues responsible for substrate binding. Biochemical studies also show that the catalytic phosphoserine of the missense variants is more stable to hydrolysis relative to wild-type enzyme. The structural perturbation resulting from mutation of this single amino acid reveals the molecular mechanism underlying PGM1 deficiency in these missense variants. DATABASE: Structural data are available in the PDB under the accession numbers 5JN5 and 5TR2. Asp263 missense variants perturb the active site of human phosphoglucomutase 1.,Stiers KM, Graham AC, Kain BN, Beamer LJ FEBS J. 2017 Jan 24. doi: 10.1111/febs.14025. PMID:28117557 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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