1hiq
From Proteopedia
(New page: 200px<br /> <applet load="1hiq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hiq" /> '''PARADOXICAL STRUCTURE AND FUNCTION IN A MUT...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1hiq.gif|left|200px]]<br /> | + | [[Image:1hiq.gif|left|200px]]<br /><applet load="1hiq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1hiq" size=" | + | |
caption="1hiq" /> | caption="1hiq" /> | ||
'''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== | ||
| Line 11: | Line 10: | ||
==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== | ||
| Line 17: | Line 16: | ||
[[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 11:01, 21 February 2008
|
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
Page seeded by OCA on Thu Feb 21 13:01:36 2008
