7evt
Crystal structure of the N-terminal degron-truncated human glutamine synthetaseCrystal structure of the N-terminal degron-truncated human glutamine synthetase
Structural highlights
DiseaseGLNA_HUMAN Defects in GLUL are the cause of congenital systemic glutamine deficiency (CSGD) [MIM:610015. CSGD is a rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine is largely absent from affected patients serum, urine and cerebrospinal fluid.[1] FunctionGLNA_HUMAN This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.[2] Publication Abstract from PubMedGlutamine synthetase (GS) is a decameric enzyme that plays a key role in nitrogen metabolism. Acetylation of the N-terminal degron (N-degron) of GS is essential for ubiquitylation and subsequent GS degradation. The full-length GS structure showed that the N-degron is buried inside the GS decamer and is inaccessible to the acetyltransferase. The structure of N-degron-truncated GS reported here reveals that the N-degron is not essential for GS decamer formation. It is also shown that the N-degron can be exposed to a solvent region through a series of conformational adjustments upon ligand binding. In summary, this study elucidated the dynamic movement of the N-degron and the possible effect of glutamine in enhancing the acetylation process. Crystal structure of N-terminal degron-truncated human glutamine synthetase.,Chek MF, Kim SY, Mori T, Kojima H, Hakoshima T Acta Crystallogr F Struct Biol Commun. 2021 Nov 1;77(Pt 11):427-434. doi:, 10.1107/S2053230X21010748. Epub 2021 Oct 29. PMID:34726182[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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