Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer

• Published in: Nature (London) 1989-04, Vol.338 (6216), p.594-596
• Main Authors: Derewenda, U, Derewenda, Z, Dodson, E. J, Dodson, G. G, Reynolds, C. D, Smith, G. D, Sparks, C, Swenson, D
• Format: Article
• Language: English
• Subjects: Biochemistry; Chemistry; Crystals; Diabetes; Exact sciences and technology; Insulin; Ions; Medical research; Molecular Sequence Data; Molecular Structure; Noncondensed benzenic compounds; Organic chemistry; Phenol; Phenols; Preparations and properties; Protein Conformation; X-Ray Diffraction; Zinc
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/338594a0

SINCE insulin was first shown by Scott to crystallize in the presence of zinc ions in 1934, a variety of Zn-containing insulin crystals have been grown. The structures of insulin in the related rhombohedral crystals of 2Zn-insulin and 4Zn-insulin have been solved 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 symmetrical 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 B1 and B8 (refs 6, 7). We report here the structure of a new symmetrical hexamer, in which all six molecules have the B1-B8 helix seen in 4Zn-insulin. Phenol molecules, found bonding specifically to each molecule, evidently stabilize this new helical conformation.