6sno

Crystal structures of human PGM1 isoform 2

spinqualitylabelsall models 6sno, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6sno 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: X-ray diffraction, Resolution 2.7Å Ligands: G1P, SEP, ZN 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) is an evolutionary conserved enzyme that belongs to the ubiquitous and ancient alpha-D-phosphohexomutases, a large enzyme superfamily with members in all three domains of life. PGM1 catalyzes the bi-directional interconversion between alpha-D-glucose 1-phosphate (G1P) and alpha-D-glucose 6-phosphate (G6P), a reaction that is essential for normal carbohydrate metabolism and also important in the cytoplasmic biosynthesis of nucleotide sugars needed for glycan biosynthesis. Clinical studies have shown that mutations in the PGM1 gene may cause PGM1 deficiency, an inborn error of metabolism previously classified as a glycogen storage disease, and PGM1 deficiency was recently also shown to be a congenital disorder of glycosylation. Here we present three crystal structures of the isoform 2 variant of PGM1, both as a free enzyme and in complex with its substrate and product. The structures show the longer N-terminal of this PGM1 variant, and the ligand complex structures reveal for the first time the detailed structural basis for both G1P substrate and G6P product recognition by human PGM1. We also show that PGM1 and the paralogous gene PGM5 are the results of a gene duplication event in a common ancestor of jawed vertebrates, and, importantly, that both PGM1 isoforms are conserved and of functional significance in all vertebrates. Our finding that PGM1 encodes two equally conserved and functionally important isoforms in the human organism should be taken into account in the evaluation of disease-related missense mutations in patients in the future. Structural basis for substrate and product recognition in human phosphoglucomutase-1 (PGM1) isoform 2, a member of the alpha-D-phosphohexomutase superfamily.,Backe PH, Laerdahl JK, Kittelsen LS, Dalhus B, Morkrid L, Bjoras M Sci Rep. 2020 Mar 27;10(1):5656. doi: 10.1038/s41598-020-62548-0. PMID:32221390 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA