Structure of insulin in 4-zinc insulin

Abstract

DURING his experiments on slow acting clinical preparations of insulin, Schlichtkrull found that a second form of rhombohedral insulin crystals appeared when the sodium chloride ion concentration in the solution was 6% or more¹. The new crystals contained four zinc ions per hexamer of insulin compared with two in the original crystals. Both forms crystallised in the space group R3 and had similar lattice constants: a=82.5 Å, c=34.0 Å for 2-zinc insulin, and a=80.7 Å, c=37.6 Å for 4-zinc insulin crystals². Both, from an early application of the rotation function³, also seemed to be very similar in structure, and to contain in each asymmetric unit, two insulin molecules related to one another by non-crystallographic twofold axes of symmetry. We have now found, from electron density calculations on 4-zinc pig insulin, that the apparent similarity of the crystal structures conceals a surprisingly large change in the conformation of one only of the two insulin molecules in the unit.