Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer

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Abstract
SINCE insulin was first shown by Scott1 to crystallize in the presence of zinc ions in 1934, a variety of Zn-containing insulin crystals have been grown2,3. The structures of insulin in the related rhombohedral crystals of 2Zn-insulin and 4Zn-insulin have been solved4,5 and reveal that the molecule is a hexamer, organized as three dimers, each containing a 2-fold symmetry axis and held together by Zn ions. In 2Zn-insulin the hexamer is nearly sym-metrical with the two axial Zn ions and the two molecules of the dimer related closely by a local 2-fold axis. But in 4Zn-insulin the two molecules in the dimer differ remarkably, creating an asymmetric 4Zn-hexamer in which one trimer is essentially equivalent to that in 2Zn-insulin and the other is different by virtue of an additional stretch of N-terminal helix between residues Bl and B8 (refs 6, 7). We report here the structure of a new sym-metrical hexamer, in which all six molecules have the B1–B8 helix seen in 4Zn-insulin. Phenol molecules, found bonding specifi-cally to each molecule, evidently stabilize this new helical conformation.

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