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| [[Image:1vkt.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1vkt| PDB=1vkt | SCENE= }} | | {{STRUCTURE_1vkt| PDB=1vkt | SCENE= }} |
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| '''HUMAN INSULIN TWO DISULFIDE MODEL, NMR, 10 STRUCTURES'''
| | ===HUMAN INSULIN TWO DISULFIDE MODEL, NMR, 10 STRUCTURES=== |
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| ==Overview==
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| Functional surfaces of a protein are often mapped by combination of X-ray crystallography and mutagenesis. Such studies of insulin have yielded paradoxical results, suggesting that the native state is inactive and reorganizes on receptor binding. Of particular interest is the N-terminal alpha-helix of the A-chain. Does this segment function as an alpha-helix or reorganize as recently proposed in a prohormone-convertase complex? To correlate structure and function, we describe a mapping strategy based on protein design. The solution structure of an engineered monomer ([AspB10, LysB28, ProB29]-human insulin) is determined at neutral pH as a template for synthesis of a novel A-chain analogue. Designed by analogy to a protein-folding intermediate, the analogue lacks the A6-A11 disulphide bridge; the cysteine residues are replaced by serine. Its solution structure is remarkable for segmental unfolding of the N-terminal A-chain alpha-helix (A1 to A8) in an otherwise native subdomain. The structure demonstrates that the overall orientation of the A and B chains is consistent with reorganization of the A-chain's N-terminal segment. Nevertheless, the analogue's low biological activity suggests that this segment, a site of clinical mutation causing diabetes mellitus, functions as a preformed recognition alpha-helix.
| | The line below this paragraph, {{ABSTRACT_PUBMED_8951384}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 8951384 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_8951384}} |
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| ==About this Structure== | | ==About this Structure== |
| 1VKT 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=1VKT OCA]. | | 1VKT 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=1VKT OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Hormone]] | | [[Category: Hormone]] |
| [[Category: Human insulin]] | | [[Category: Human insulin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:39:23 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:43:55 2008'' |
