Download MendeleyRole of C-terminal B-chain residues in insulin assembly: the structure of hexameric LysB28ProB29-human insulin.
Ciszak, E., Beals, J.M., Frank, B.H., Baker, J.C., Carter, N.D., Smith, G.D.(1995) Structure 3: 615-622
- PubMed: 8590022
- DOI: https://doi.org/10.1016/s0969-2126(01)00195-2
- Primary Citation of Related Structures:
1LPH - PubMed Abstract:
LysB28ProB29-human insulin (Humalog), a fully potent insulin analog in which the prolyl, lysyl sequence at the C-terminal end of the B-chain is inverted, exhibits a decreased association of monomers to dimers leading to rapid in vivo absorption. This provides important benefits for the insulin-requiring diabetic. In spite of its monomeric nature, LysB28ProB29-human insulin can exist as a discrete hexameric structure in the presence of both zinc and phenol. Studies of the crystal structure of LysB28ProB29-human insulin in a hexameric complex were initiated to gain a molecular understanding of the effect of the sequence inversion on the analog's self-association properties and, consequently, its in vivo efficacy.
Organizational Affiliation:
Hauptman-Woodward Medical Research Institute, Inc., Buffalo, NY 14203, USA.
