Studies on the crystal structure of A1-(L-tryptophan) insulin at 2.1 A resolution.

In order to study the biological effect of alterations to the N-terminus of the insulin A-chain, we have determined the crystal structure of A1-(L-Trp) insulin and discovered that it belongs to the trigonal system with space group R3. The parameters of the unit cell are a = b = 80.3A, c = 37.5A. The model was adjusted and refined by using a stereochemically-restrained least squares program, assisted by manual revision of the model based on the difference Fourier map, to a final R-factor of 0.195. The main and side chains of both A1-(L-Trp) residues in the asymmetric unit are well ordered. It was found that the A1-Trp residue of molecule I occupied two distinct positions. We have proposed from the results of the three-dimensional structure that the 4-zinc insulin hexameric form is a stored state of insulin molecules in a conformation of low activity. The structural details of the insulin molecule and its structure and function relationship have also been discussed.