5vin

Crystal Structure of the R515Q missense variant of human PGM1

spinqualitylabelsall models 5vin, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5vin is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CO, GOL, SO4 Related: 5epc Gene: PGM1 (HUMAN) Activity: Phosphoglucomutase, with EC number 5.4.2.2 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 Human phosphoglucomutase 1 (PGM1) plays a central role in cellular glucose homeostasis, catalyzing the conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, missense variants of this enzyme were identified as causing an inborn error of metabolism, PGM1 deficiency, with features of a glycogen storage disease and a congenital disorder of glycosylation. Previous studies of selected PGM1 variants have revealed various mechanisms for enzyme dysfunction, including regions of structural disorder and side-chain rearrangements within the active site. Here, we examine variants within a substrate-binding loop in domain 4 (D4) of PGM1 that cause extreme impairment of activity. Biochemical, structural, and computational studies demonstrate multiple detrimental impacts resulting from these variants, including loss of conserved ligand-binding interactions and reduced mobility of the D4 loop, due to perturbation of its conformational ensemble. These potentially synergistic effects make this conserved ligand-binding loop a hotspot for disease-related variants in PGM1 and related enzymes. A Hotspot for Disease-Associated Variants of Human PGM1 Is Associated with Impaired Ligand Binding and Loop Dynamics.,Stiers KM, Beamer LJ Structure. 2018 Aug 7. pii: S0969-2126(18)30251-X. doi:, 10.1016/j.str.2018.07.005. PMID:30122451 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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