1vkt
From Proteopedia
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| - | [[Image:1vkt.jpg|left|200px]] | + | [[Image:1vkt.jpg|left|200px]] |
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| - | '''HUMAN INSULIN TWO DISULFIDE MODEL, NMR, 10 STRUCTURES''' | + | {{Structure |
| + | |PDB= 1vkt |SIZE=350|CAPTION= <scene name='initialview01'>1vkt</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''HUMAN INSULIN TWO DISULFIDE MODEL, NMR, 10 STRUCTURES''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1VKT is a [ | + | 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]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/8951384 8951384] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: human insulin]] | [[Category: human insulin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:46:57 2008'' |
Revision as of 12:46, 20 March 2008
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HUMAN INSULIN TWO DISULFIDE MODEL, NMR, 10 STRUCTURES
Contents |
Overview
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.
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
1VKT is a Protein complex structure of sequences from Homo sapiens. Full crystallographic 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 Thu Mar 20 14:46:57 2008
