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