Derewenda U, Derewenda Z, Dodson E J, Dodson G G, Reynolds C D, Smith G D, Sparks C, Swenson D
Chemistry Department, York University, UK.
Nature. 1989 Apr 13;338(6216):594-6. 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.
自1934年斯科特首次证明胰岛素在锌离子存在下可结晶以来，已生长出多种含锌胰岛素晶体。已解析出2Zn-胰岛素和4Zn-胰岛素相关菱形晶体中胰岛素的结构，结果显示该分子为六聚体，由三个二聚体组成，每个二聚体包含一个二重对称轴，并通过锌离子结合在一起。在2Zn-胰岛素中，六聚体与两个轴向锌离子几乎对称，二聚体的两个分子通过局部二重轴紧密相关。但在4Zn-胰岛素中，二聚体中的两个分子差异显著，形成了一个不对称的4Zn-六聚体，其中一个三聚体与2Zn-胰岛素中的基本相同，另一个则因B1和B8残基之间额外的N端螺旋延伸而不同（参考文献6、7）。我们在此报告一种新的对称六聚体的结构，其中所有六个分子都具有4Zn-胰岛素中所见的B1-B8螺旋。发现酚分子与每个分子特异性结合，显然稳定了这种新的螺旋构象。
