1HIQ: PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS

Citation:
Abstract
The solution structure of a diabetes-associated mutant human insulin (insulin Los Angeles; PheB24-->Ser) was determined by 13C-edited NMR spectroscopy and distance-geometry/simulated annealing calculations. Among vertebrate insulins PheB24 is invariant, and in crystal structures the aromatic ring appears to anchor the putative receptor-binding surface through long-range packing interactions in the hydrophobic core. B24 substitutions are of particular interest in relation to the mechanism of receptor binding. In one analogue ([GlyB24]insulin), partial unfolding of the B chain has been observed with paradoxical retention of near-native bioactivity. The present study of [SerB24]insulin extends this observation: relative to [GlyB24]insulin, near-native structure is restored despite significant loss of function. To our knowledge, our results provide the first structural study of a diabetes-associated mutant insulin and support the hypothesis that insulin undergoes a change in conformation on receptor binding.
PDB ID: 1HIQDownload
MMDB ID: 1193
PDB Deposition Date: 1993/3/5
Updated in MMDB: 2017/12
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 1HIQ: dimeric; determined by author
Molecular Components in 1HIQ
Label Count Molecule
Proteins (2 molecules)
1
Insulin(Gene symbol: INS)
Molecule annotation
1
Insulin(Gene symbol: INS)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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