2jmn

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{{STRUCTURE_2jmn| PDB=2jmn | SCENE= }}
{{STRUCTURE_2jmn| PDB=2jmn | SCENE= }}
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'''NMR structure of human insulin mutant His-B10-Asp, Pro-B28-Lys, Lys-B29-Pro, 20 structures'''
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===NMR structure of human insulin mutant His-B10-Asp, Pro-B28-Lys, Lys-B29-Pro, 20 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}}
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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2JMN is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1vks 1vks]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JMN OCA].
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2JMN is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1vks 1vks]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JMN OCA].
==Reference==
==Reference==
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[[Category: Human insulin]]
[[Category: Human insulin]]
[[Category: Mutant]]
[[Category: Mutant]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:02:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:51:21 2008''

Revision as of 01:51, 29 July 2008

Image:2jmn.png

Template:STRUCTURE 2jmn

Contents

NMR structure of human insulin mutant His-B10-Asp, Pro-B28-Lys, Lys-B29-Pro, 20 structures

Template:ABSTRACT PUBMED 8951384

Disease

Known disease associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]

About this Structure

2JMN is a Protein complex structure of sequences from Homo sapiens. This structure supersedes the now removed PDB entries and 1vks. 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 04:51:21 2008

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OCA

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