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Structure of porcine insulin cocrystallized with clupeine Z.

Balschmidt P, Hansen FB, Dodson EJ, Dodson GG, Korber F
Acta Crystallogr B 47 ( Pt 6) 975-86 (1991)
Cited: 17 times
EuropePMC logo PMID: 1772633

Abstract

The crystal structure of NPH-insulin, pig insulin cocrystallized with zinc, m-cresol and protamine, has been solved by molecular replacement and refined using restrained least-squares refinement methods. The final crystallographic R factor for all reflections between 2 and 10 A is 19.4%. The insulin molecules are arranged as hexamers with two tetrahedrally coordinated Zn atoms in the central channel and one m-cresol bound to each monomer near His B5. One protamine binding site has been unequivocally identified near a dimer-dimer interface, although most of the polypeptide is crystallographically disordered. The conformation of the insulin moiety and the structural differences between the three unique monomers have been analysed. The zinc and m-cresol environments are described and the nature of the protamine binding site is outlined.

Reviews - 7ins mentioned but not cited (3)

  1. Breaking symmetry in protein dimers: designs and functions. Brown JH. Protein Sci. 15 1-13 (2006)
  2. In Quest for Improved Drugs against Diabetes: The Added Value of X-ray Powder Diffraction Methods. Karavassili F, Valmas A, Fili S, Georgiou CD, Margiolaki I. Biomolecules 7 (2017)
  3. Structural principles of insulin formulation and analog design: A century of innovation. Jarosinski MA, Dhayalan B, Chen YS, Chatterjee D, Varas N, Weiss MA. Mol Metab 52 101325 (2021)

Articles - 7ins mentioned but not cited (2)

  1. The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity. Lou M, Garrett TP, McKern NM, Hoyne PA, Epa VC, Bentley JD, Lovrecz GO, Cosgrove LJ, Frenkel MJ, Ward CW. Proc. Natl. Acad. Sci. U.S.A. 103 12429-12434 (2006)
  2. Computing the protein binding sites. Guo F, Wang L. BMC Bioinformatics 13 Suppl 10 S2 (2012)


Reviews citing this publication (3)

  1. Absorption kinetics of insulin after subcutaneous administration. Søeborg T, Rasmussen CH, Mosekilde E, Colding-Jørgensen M. Eur J Pharm Sci 36 78-90 (2009)
  2. Bioavailability and variability of biphasic insulin mixtures. Søeborg T, Rasmussen CH, Mosekilde E, Colding-Jørgensen M. Eur J Pharm Sci 46 198-208 (2012)
  3. Solid-state protein formulations. Angkawinitwong U, Sharma G, Khaw PT, Brocchini S, Williams GR. Ther Deliv 6 59-82 (2015)

Articles citing this publication (9)

  1. Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase e. Lou H, Kim SK, Zaitsev E, Snell CR, Lu B, Loh YP. Neuron 45 245-255 (2005)
  2. Hybrid insulin cocrystals for controlled release delivery. Brader ML, Sukumar M, Pekar AH, McClellan DS, Chance RE, Flora DB, Cox AL, Irwin L, Myers SR. Nat. Biotechnol. 20 800-804 (2002)
  3. Preparation and characterization of a cocrystalline suspension of [LysB28,ProB29]-human insulin analogue. DeFelippis MR, Bakaysa DL, Bell MA, Heady MA, Li S, Pye S, Youngman KM, Radziuk J, Frank BH. J Pharm Sci 87 170-176 (1998)
  4. Structural studies of a crystalline insulin analog complex with protamine by atomic force microscopy. Yip CM, Brader ML, Frank BH, DeFelippis MR, Ward MD. Biophys. J. 78 466-473 (2000)
  5. Helical structure of basic proteins from spermatozoa. Comparison with model peptides. Verdaguer N, Perelló M, Palau J, Subirana JA. Eur. J. Biochem. 214 879-887 (1993)
  6. Structural characterization of insulin NPH formulations. Norrman M, Hubálek F, Schluckebier G. Eur J Pharm Sci 30 414-423 (2007)
  7. Crystallographic characterization of two novel crystal forms of human insulin induced by chaotropic agents and a shift in pH. Norrman M, Schluckebier G. BMC Struct. Biol. 7 83 (2007)
  8. A novel protein cross-linking reaction in stressed Neutral Protamine Hagedorn formulations of insulin. Beavis RC, Kneirman MD, Sharknas D, Heady MA, Frank BH, DeFelippis MR. J Pharm Sci 88 331-336 (1999)
  9. Reversible adsorption of soluble hexameric insulin onto the surface of insulin crystals cocrystallized with protamine: an electrostatic interaction. Dodd SW, Havel HA, Kovach PM, Lakshminarayan C, Redmon MP, Sargeant CM, Sullivan GR, Beals JM. Pharm. Res. 12 60-68 (1995)


Related citations provided by authors (2)

  1. Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer.. Derewenda U, Derewenda Z, Dodson EJ, Dodson GG, Reynolds CD, Smith GD, Sparks C, Swenson D Nature 338 594-6 (1989)
  2. The Structure of 2Zn Pig Insulin Crystals at 1.5 Angstroms Resolution. Baker EN, Blundell TL, Cutfield JF, Cutfield SM, Dodson EJ, Dodson GG, Hodgkin DMC, Hubbard RE, Isaacs NW, Reynolds CD, Sakabe K, Sakabe N, Vijayan NM Philos. Trans. R. Soc. London,Ser. B 319 369- (1988)

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