6php

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Crystal structure of glucagon analog with 4-bromo-phenylalanine substitutions at position 6 and 22 in space group I41 at 1.65 A resolution

Structural highlights

6php 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 1.65Å
Ligands:4BF
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.[1] [2] [3] 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.[4] [5] [6] 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.[7] [8] [9] 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.[10] [11] [12] 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.[13] [14] [15]

See Also

References

  1. ↑ Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61. PMID:8482423
  2. ↑ Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701. PMID:14557443
  3. ↑ Tadokoro R, Shimizu T, Hosaka A, Kaneko N, Satoh Y, Yamashiro Y. Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. Acta Paediatr. 2003 Oct;92(10):1175-9. PMID:14632334
  4. ↑ Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61. PMID:8482423
  5. ↑ Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701. PMID:14557443
  6. ↑ Tadokoro R, Shimizu T, Hosaka A, Kaneko N, Satoh Y, Yamashiro Y. Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. Acta Paediatr. 2003 Oct;92(10):1175-9. PMID:14632334
  7. ↑ Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61. PMID:8482423
  8. ↑ Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701. PMID:14557443
  9. ↑ Tadokoro R, Shimizu T, Hosaka A, Kaneko N, Satoh Y, Yamashiro Y. Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. Acta Paediatr. 2003 Oct;92(10):1175-9. PMID:14632334
  10. ↑ Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61. PMID:8482423
  11. ↑ Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701. PMID:14557443
  12. ↑ Tadokoro R, Shimizu T, Hosaka A, Kaneko N, Satoh Y, Yamashiro Y. Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. Acta Paediatr. 2003 Oct;92(10):1175-9. PMID:14632334
  13. ↑ Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes. 1993 May;42(5):658-61. PMID:8482423
  14. ↑ Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701. PMID:14557443
  15. ↑ Tadokoro R, Shimizu T, Hosaka A, Kaneko N, Satoh Y, Yamashiro Y. Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants. Acta Paediatr. 2003 Oct;92(10):1175-9. PMID:14632334

Contents


PDB ID 6php

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