7qqh | pdb_00007qqh

Crystal structure of MYORG (D520N) in complex with Gal-a1,4-Glc

spinqualitylabelsall models 7qqh, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7qqh is a 4 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 2.25Å Ligands: BGC, EDO, GLA, MLI, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease MYORG_HUMAN Bilateral striopallidodentate calcinosis. The disease is caused by variants affecting the gene represented in this entry. Function MYORG_HUMAN Putative glycosidase. Promotes myogenesis by activating AKT signaling through the maturation and secretion of IGF2.[UniProtKB:Q69ZQ1] Publication Abstract from PubMed Primary familial brain calcification (PFBC) is characterised by abnormal deposits of calcium phosphate within various regions of the brain that are associated with severe cognitive impairments, psychiatric conditions, and movement disorders. Recent studies in diverse populations have shown a link between mutations in myogenesis-regulating glycosidase (MYORG) and the development of this disease. MYORG is a member of glycoside hydrolase (GH) family 31 (GH31) and, like the other mammalian GH31 enzyme alpha-glucosidase II, this enzyme is found in the lumen of the endoplasmic reticulum (ER). Though presumed to act as an alpha-glucosidase due to its localization and sequence relatedness to alpha-glucosidase II, MYORG has never been shown to exhibit catalytic activity. Here, we show that MYORG is an alpha-galactosidase and present the high-resolution crystal structure of MYORG in complex with substrate and inhibitor. Using these structures, we map detrimental mutations that are associated with MYORG-associated brain calcification and define how these mutations may drive disease progression through loss of enzymatic activity. Finally, we also detail the thermal stabilisation of MYORG afforded by a clinically approved small molecule ligand, opening the possibility of using pharmacological chaperones to enhance the activity of mutant forms of MYORG. The primary familial brain calcification-associated protein MYORG is an alpha-galactosidase with restricted substrate specificity.,Meek RW, Brockerman J, Fordwour OB, Zandberg WF, Davies GJ, Vocadlo DJ PLoS Biol. 2022 Sep 21;20(9):e3001764. doi: 10.1371/journal.pbio.3001764. , eCollection 2022 Sep. PMID:36129849 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA