I222 crystal form of despentapeptide (B26–B30) insulin provides new insights into the properties of monomeric insulin
✍ Scribed by Whittingham, Jean L. ;Youshang, Zhang ;Žáková, Lenka ;Dodson, Eleanor J. ;Turkenburg, Johan P. ;Brange, Jens ;Dodson, G. Guy
- Publisher
- International Union of Crystallography
- Year
- 2006
- Tongue
- English
- Weight
- 914 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0907-4449
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✦ Synopsis
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 A spacing (space group I222) revealed that the DPI molecule, which is unable to make beta-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 alpha-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 T(6) 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 A displacement of the B20-B23 beta-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.