Despentapeptide (des-B26-B30) insulin (DPI), an active modified insulin, has been crystallized in the presence of 20% acetic acid pH 2. A crystal structure analysis to 1.8 Å spacing (space group I222) revealed that the DPI molecule, which is unable to make β-strand interactions for physiological dimer formation and is apparently monomeric in solution, formed an alternative lattice-generated dimer. The formation of this dimer involved interactions between surfaces which included the B9-B19 α-helices (usually buried by the dimer-dimer contacts within the native hexamer). The two crystallographically independent molecules within the dimer were essentially identical and were similar in conformation to T-state insulin as seen in the T6 insulin hexamer. An unusual feature of each molecule in the dimer was the presence of two independent conformations at the B-chain C-terminus (residues B20-B25). Both conformations were different from that of native insulin, involving a 3.5 Å displacement of the B20-B23 β-turn and a repositioning of residue PheB25 such that it made close van der Waals contact with the main body of the molecule, appearing to stabilize the B-chain C-terminus. © 2006 International Union of Crystallography - all rights reserved.
Whittingham, J. L., Youshang, Z., Žáková, L., Dodson, E. J., Turkenburg, J. P., Brange, J., & Dodson, G. G. (2006). I222 crystal form of despentapeptide (B26-B30) insulin provides new insights into the properties of monomeric insulin. Acta Crystallographica Section D: Biological Crystallography, 62(5), 505–511. https://doi.org/10.1107/S0907444906006871