Abstract
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 angstrom spacing (space group I222) revealed that the DPI molecule, which is unable to make beta-strand interactions for physio-logical 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 angstrom 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.
| Original language | English |
|---|---|
| Pages (from-to) | 505-511 |
| Number of pages | 7 |
| Journal | Acta crystallographica section d-Biological crystallography |
| Volume | 62 |
| DOIs | |
| Publication status | Published - May 2006 |
Keywords
- STRUCTURAL SWITCH
- RECEPTOR-BINDING
- SIDE-CHAIN
- MAIN-CHAIN
- PH
- SPECTROSCOPY
- REFINEMENT
- RESOLUTION
- RESIDUES
- SOLVENT