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1vkt

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[[Image:1vkt.jpg|left|200px]]
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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 8951384 is the PubMed ID number.
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{{ABSTRACT_PUBMED_8951384}}
==About this Structure==
==About this Structure==
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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].
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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].
==Reference==
==Reference==
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[[Category: Hormone]]
[[Category: Hormone]]
[[Category: Human insulin]]
[[Category: Human insulin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:39:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:43:55 2008''

Revision as of 23:43, 28 July 2008

Template:STRUCTURE 1vkt

HUMAN INSULIN TWO DISULFIDE MODEL, NMR, 10 STRUCTURES

Template:ABSTRACT PUBMED 8951384

About this Structure

1VKT is a Protein complex structure of sequences from Homo sapiens. Full experimental information is available from OCA.

Reference

Mapping the functional surface of insulin by design: structure and function of a novel A-chain analogue., Hua QX, Hu SQ, Frank BH, Jia W, Chu YC, Wang SH, Burke GT, Katsoyannis PG, Weiss MA, J Mol Biol. 1996 Nov 29;264(2):390-403. PMID:8951384

Page seeded by OCA on Tue Jul 29 02:43:55 2008

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