1hiq
| |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS
OverviewOverview
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.
About this StructureAbout this Structure
1HIQ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus., Hua QX, Shoelson SE, Inouye K, Weiss MA, Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):582-6. PMID:8421693
Page seeded by OCA on Sun Mar 30 21:05:44 2008