1hiq: Difference between revisions
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'''PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS''' | '''PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS''' | ||
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[[Category: Shoelson, S E.]] | [[Category: Shoelson, S E.]] | ||
[[Category: Weiss, M A.]] | [[Category: Weiss, M A.]] | ||
[[Category: | [[Category: Hormone]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:53:06 2008'' | |||
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Revision as of 18:53, 2 May 2008
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 Fri May 2 18:53:06 2008