1hiq: Difference between revisions
New page: left|200px<br /> <applet load="1hiq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hiq" /> '''PARADOXICAL STRUCTURE AND FUNCTION IN A MUT... |
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'''PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS'''<br /> | '''PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS'''<br /> | ||
==Overview== | ==Overview== | ||
The solution structure of a diabetes-associated mutant human insulin | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1HIQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1HIQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HIQ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Hua, Q | [[Category: Hua, Q X.]] | ||
[[Category: Inouye, K.]] | [[Category: Inouye, K.]] | ||
[[Category: Shoelson, S | [[Category: Shoelson, S E.]] | ||
[[Category: Weiss, M | [[Category: Weiss, M A.]] | ||
[[Category: hormone]] | [[Category: hormone]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:01:36 2008'' | ||
Revision as of 14:01, 21 February 2008
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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.
DiseaseDisease
Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]
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
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