title: Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer.
abstract: 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.
authors.affiliation: Chemistry Department, York University, UK.
authors.forename: U
authors.initials: U
authors.lastname: Derewenda
authors.forename: Z
authors.initials: Z
authors.lastname: Derewenda
authors.forename: E J
authors.initials: EJ
authors.lastname: Dodson
authors.forename: G G
authors.initials: GG
authors.lastname: Dodson
authors.forename: C D
authors.initials: CD
authors.lastname: Reynolds
authors.forename: G D
authors.initials: GD
authors.lastname: Smith
authors.forename: C
authors.initials: C
authors.lastname: Sparks
authors.forename: D
authors.initials: D
authors.lastname: Swenson
mesh_terms: D007328:Insulin; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019800:Phenol; D010636:Phenols; D011487:Protein Conformation; D014961:X-Ray Diffraction; D015032:Zinc
chemical_list: D007328:Insulin; D010636:Phenols; D019800:Phenol; D015032:Zinc