1k3m

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[[Image:1k3m.gif|left|200px]]
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{{STRUCTURE_1k3m| PDB=1k3m | SCENE= }}
{{STRUCTURE_1k3m| PDB=1k3m | SCENE= }}
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'''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES'''
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===NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES===
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==Overview==
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To investigate the cooperativity of insulin's structure, a cavity-forming substitution was introduced within the hydrophobic core of an engineered monomer. The substitution, Ile(A2)--&gt;Ala in the A1-A8 alpha-helix, does not impair disulfide pairing between chains. In accord with past studies of cavity-forming mutations in globular proteins, a decrement was observed in thermodynamic stability (DeltaDeltaG(u) 0.4-1.2 kcal/mole). Unexpectedly, CD studies indicate an attenuated alpha-helix content, which is assigned by NMR spectroscopy to selective destabilization of the A1-A8 segment. The analog's solution structure is otherwise similar to that of native insulin, including the B chain's supersecondary structure and a major portion of the hydrophobic core. Our results show that (1) a cavity-forming mutation in a globular protein can lead to segmental unfolding, (2) tertiary packing of Ile(A2), a residue of low helical propensity, stabilizes the A1-A8 alpha-helix, and (3) folding of this segment is not required for native disulfide pairing or overall structure. We discuss these results in relation to a hierarchical pathway of protein folding and misfolding. The Ala(A2) analog's low biological activity (0.5% relative to the parent monomer) highlights the importance of the A1-A8 alpha-helix in receptor recognition.
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(as it appears on PubMed at http://www.pubmed.gov), where 11742127 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11742127}}
==About this Structure==
==About this Structure==
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1K3M is a [[Protein complex]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K3M OCA].
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1K3M is a [[Protein complex]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K3M 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 Fri May 2 22:15:43 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 02:23:36 2008''

Revision as of 03:01, 2 July 2008

Template:STRUCTURE 1k3m

NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES

Template:ABSTRACT PUBMED 11742127

About this Structure

1K3M is a Protein complex structure. Full experimental information is available from OCA.

Reference

A cavity-forming mutation in insulin induces segmental unfolding of a surrounding alpha-helix., Xu B, Hua QX, Nakagawa SH, Jia W, Chu YC, Katsoyannis PG, Weiss MA, Protein Sci. 2002 Jan;11(1):104-16. PMID:11742127

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