6nzn | pdb_00006nzn

Dimer-of-dimer amyloid fibril structure of glucagon

spinqualitylabelsall models 6nzn Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6nzn is a 16 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLUC_HUMAN Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis. GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability. Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness. Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life. Publication Abstract from PubMed Glucagon and insulin maintain blood glucose homeostasis and are used to treat hypoglycemia and hyperglycemia, respectively, in patients with diabetes. Whereas insulin is stable for weeks in its solution formulation, glucagon fibrillizes rapidly at the acidic pH required for solubility and is therefore formulated as a lyophilized powder that is reconstituted in an acidic solution immediately before use. Here we use solid-state NMR to determine the atomic-resolution structure of fibrils of synthetic human glucagon grown at pharmaceutically relevant low pH. Unexpectedly, two sets of chemical shifts are observed, indicating the coexistence of two beta-strand conformations. The two conformations have distinct water accessibilities and intermolecular contacts, indicating that they alternate and hydrogen bond in an antiparallel fashion along the fibril axis. Two antiparallel beta-sheets assemble with symmetric homodimer cross sections. This amyloid structure is stabilized by numerous aromatic, cation-pi, polar and hydrophobic interactions, suggesting mutagenesis approaches to inhibit fibrillization could improve this important drug. The peptide hormone glucagon forms amyloid fibrils with two coexisting beta-strand conformations.,Gelenter MD, Smith KJ, Liao SY, Mandala VS, Dregni AJ, Lamm MS, Tian Y, Xu W, Pochan DJ, Tucker TJ, Su Y, Hong M Nat Struct Mol Biol. 2019 Jul;26(7):592-598. doi: 10.1038/s41594-019-0238-6. Epub, 2019 Jun 24. PMID:31235909 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glucagon

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