2kqp

NMR Structure of ProinsulinNMR Structure of Proinsulin

Structural highlights 2kqp is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: INS (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Disease [INS_HUMAN] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:176730]. Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:125852]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:606176]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy. Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:613370]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. Function [INS_HUMAN] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Mutations that impair folding cause neonatal diabetes mellitus. Although the classical structure of insulin is well established, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to characterize a monomeric analogue. Proinsulin contains a native-like insulin moiety (A- and B-domains); the tethered connecting (C) domain (as probed by {(1)H}-(15)N nuclear Overhauser enhancements) is progressively less ordered. Although the BC junction is flexible, residues near the CA junction exhibit alpha-helical-like features. Relative to canonical alpha-helices, however, segmental (13)C(alpha/beta) chemical shifts are attenuated, suggesting that this junction and contiguous A-chain residues are molten. We propose that flexibility at each C-domain junction facilitates prohormone processing. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection. The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus. Solution structure of proinsulin: connecting domain flexibility and prohormone processing.,Yang Y, Hua QX, Liu J, Shimizu EH, Choquette MH, Mackin RB, Weiss MA J Biol Chem. 2010 Mar 12;285(11):7847-51. Epub 2010 Jan 27. PMID:20106974 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Molecular Playground/Insulin

spinqualitylabelsall models 2kqp, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image