2jmn: Difference between revisions
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New page: left|200px<br /> <applet load="2jmn" size="450" color="white" frame="true" align="right" spinBox="true" caption="2jmn" /> '''NMR structure of human insulin mutant His-B... |
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[[Image:2jmn.gif|left|200px]]<br /> | [[Image:2jmn.gif|left|200px]]<br /><applet load="2jmn" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''NMR structure of human insulin mutant His-B10-Asp, Pro-B28-Lys, Lys-B29-Pro, 20 structures'''<br /> | '''NMR structure of human insulin mutant His-B10-Asp, Pro-B28-Lys, Lys-B29-Pro, 20 structures'''<br /> | ||
==Overview== | ==Overview== | ||
Functional surfaces of a protein are often mapped by combination of X-ray | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2JMN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure | 2JMN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entries 1LNP and 1VKS. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JMN OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Burke, G | [[Category: Burke, G T.]] | ||
[[Category: Chu, Y | [[Category: Chu, Y C.]] | ||
[[Category: Frank, B | [[Category: Frank, B H.]] | ||
[[Category: Hu, S | [[Category: Hu, S Q.]] | ||
[[Category: Hua, Q | [[Category: Hua, Q X.]] | ||
[[Category: Jia, W | [[Category: Jia, W H.]] | ||
[[Category: Katsoyannis, P | [[Category: Katsoyannis, P G.]] | ||
[[Category: Wang, S | [[Category: Wang, S H.]] | ||
[[Category: Weiss, M | [[Category: Weiss, M A.]] | ||
[[Category: hormone]] | [[Category: hormone]] | ||
[[Category: human insulin]] | [[Category: human insulin]] | ||
[[Category: mutant]] | [[Category: mutant]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:04:05 2008'' | ||
