1hiq
From Proteopedia
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PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]
About this Structure
1HIQ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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