1k3m: Difference between revisions
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[[Image:1k3m.gif|left|200px]] | [[Image:1k3m.gif|left|200px]] | ||
'''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES''' | {{Structure | ||
|PDB= 1k3m |SIZE=350|CAPTION= <scene name='initialview01'>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''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1K3M is a [ | 1K3M is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K3M OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11742127 11742127] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Chu, Y C.]] | [[Category: Chu, Y C.]] | ||
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[[Category: mutant]] | [[Category: mutant]] | ||
''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 12:12:07 2008'' | ||
Revision as of 10:12, 20 March 2008
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NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES
Overview
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)-->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.
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
1K3M is a Protein complex structure of sequences from [1]. Full crystallographic 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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