Destripeptide (B28-B30) insulin (DTRI) is an insulin analogue that has much
weaker association ability than native insulin but keeps most of its biolo
gical activity. It can be crystallized from a solution containing zinc ions
at near-neutral pH. Its crystal structure has been determined by molecular
replacement and refined at 1.9 Angstrom resolution. DTRI in the crystal ex
ists as a loose hexamer compared with 2Zn insulin. The hexamer only contain
s one zinc ion that coordinates to the B10 His residues of three monomers.
Although residues B28-B30 are located in the monomer-monomer interface with
in a dimer, the removal of them can simultaneously weaken both the interact
ions between monomers within the dimer and the interactions between dimers.
Because the B-chain C-terminus of insulin is very flexible, we take the DT
RI hexamer as a transition state in the native insulin dissociation process
and suggest a possible dissociation process of the insulin hexamer based o
n the DTRI structure. (C) 2001 Elsevier Science B.V. All rights reserved.