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| [[Image:2hho.gif|left|200px]] | | {{Seed}} |
| | [[Image:2hho.png|left|200px]] |
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| {{STRUCTURE_2hho| PDB=2hho | SCENE= }} | | {{STRUCTURE_2hho| PDB=2hho | SCENE= }} |
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| '''NMR structure of human insulin mutant GLY-B8-SER, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures'''
| | ===NMR structure of human insulin mutant GLY-B8-SER, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures=== |
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| ==Overview==
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| How insulin binds to the insulin receptor has long been a subject of speculation. Although the structure of the free hormone has been extensively characterized, a variety of evidence suggests that a conformational change occurs upon receptor binding. Here, we employ chiral mutagenesis, comparison of corresponding d and l amino acid substitutions, to investigate a possible switch in the B-chain. To investigate the interrelation of structure, function, and stability, isomeric analogs have been synthesized in which an invariant glycine in a beta-turn (Gly(B8)) is replaced by d- or l-Ser. The d substitution enhances stability (DeltaDeltaG(u) 0.9 kcal/mol) but impairs receptor binding by 100-fold; by contrast, the l substitution markedly impairs stability (DeltaDeltaG(u) -3.0 kcal/mol) with only 2-fold reduction in receptor binding. Although the isomeric structures each retain a native-like overall fold, the l-Ser(B8) analog exhibits fewer helix-related and long range nuclear Overhauser effects than does the d-Ser(B8) analog or native monomer. Evidence for enhanced conformational fluctuations in the unstable analog is provided by its attenuated CD spectrum. The inverse relationship between stereospecific stabilization and receptor binding strongly suggests that the B7-B10 beta-turn changes conformation on receptor binding.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16762918}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16762918 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16762918}} |
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| ==Disease== | | ==Disease== |
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| ==About this Structure== | | ==About this Structure== |
| 2HHO is a [[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=2HHO OCA]. | | 2HHO is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HHO OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Human insulin]] | | [[Category: Human insulin]] |
| [[Category: Mutant]] | | [[Category: Mutant]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:18:23 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:57:14 2008'' |
