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Structure of insulin in 4-zinc insulin

Structure of insulin in 4-zinc insulin,10.1038/261166a0,Nature,Graham Bentley,Eleanor Dodson,Guy Dodson,Dorothy Hodgkin,Dan Mercola

Structure of insulin in 4-zinc insulin   (Citations: 57)
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DURING his experiments on slow acting clinical preparations of insulin, Schlichtkrull found that a second form of rhombohedral insulin crystals appeared when the sodium chloride ion concentration in the solution was 6% or more1. The new crystals contained four zinc ions per hexamer of insulin compared with two in the original crystals. Both forms crystallised in the space group R3 and had similar lattice constants: a=82.5 Å, c=34.0 Å for 2-zinc insulin, and a=80.7 Å, c=37.6 Å for 4-zinc insulin crystals2. Both, from an early application of the rotation function3, also seemed to be very similar in structure, and to contain in each asymmetric unit, two insulin molecules related to one another by non-crystallographic twofold axes of symmetry. We have now found, from electron density calculations on 4-zinc pig insulin, that the apparent similarity of the crystal structures conceals a surprisingly large change in the conformation of one only of the two insulin molecules in the unit.
Journal: Nature , vol. 261, no. 5556, pp. 166-168, 1976
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    • ...The results of the mass spectrometric analysis of zinc are summarized in Table II. The molar ratio of insulin:Zn changed during the preparation of the hyaluronan-insulin complex . The native, rDNA-derived insulin had a ratio of about 3, which is in line with the ratios of crystallized insulin, containing two hexameric forms, of 6:2 and 6:4 (19)...
    • ...It has been reported that removal of zinc from insulin results in a reversible state of structural flexibility and also that the presence of zinc in the molecule may be an important factor in its hypoglycemic activity, which is more prolonged for 4-zinc insulin than for 2-zinc insulin (19)...
    • ...Native pig 4-zinc insulin (hexameric) (19) — 1.5 Native pig 2-zinc insulin (hexameric) (19) — 3.0...
    • ...Native pig 4-zinc insulin (hexameric) (19) — 1.5 Native pig 2-zinc insulin (hexameric) (19) — 3.0...

    Gustaf Jederstromet al. Formulating Insulin for Oral Administration: Preparation of Hyaluronan...

    • ...For this preliminary study we have selected insulin (PDB code 1ZNI) (Bentley et al. 1976) as a prototype for establishing our simulation and analysis procedures...
    • ...X-ray crystallographic studies of hexameric and dimeric insulin have shown several conformational states for the N-terminus of chain B (Badger et al. 1991; Bentley et al. 1976; Ciszak et al. 1995; Derewenda et al. 1989; Yao et al. 1999)...

    A. Budiet al. Effect of external stresses on protein conformation: a computer modell...

    • ...Moreover, a histidine residue at B10 in insulin has been demonstrated as being essential for the binding of zinc in the hexamer structure (Bently et al. 1976), and is found at an equivalent position in Ley I-L (Fig. 2). A comparison between the complete amino acid sequence of human and porcine pro Ley I-L reveals a similarity of about 70%...

    E. Burkhardtet al. A human cDNA coding for the Leydig insulin-like peptide (Ley IL)

    • ...[17]. The most fully occupied new site is at the hexamer centre between the two B13 glutamic acid sidechains paired together by the association of insulin dimers in the hexamer (Fig. 1). At lower pH (6.0 - 6.5) divalent metal ion binding still occurs at this site but is reduced at the other sites (Dodson, unpublished)...
    • ...As soon as a sufficient number of proinsulin molecules inside the rough endoplasmic reticulum are released from their N-terminal extensions they will, after folding, presumably assemble into hexamers in which two or four zinc ions are centrally coordinated provided enough zinc is present [17]...

    S. O. Emdinet al. Role of zinc in insulin biosynthesis

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