1k3m
From Proteopedia
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'''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES''' | '''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES''' | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1K3M is a [[Protein complex]] structure | + | 1K3M is a [[Protein complex]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K3M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Weiss, M A.]] | [[Category: Weiss, M A.]] | ||
[[Category: Xu, B.]] | [[Category: Xu, B.]] | ||
| - | [[Category: | + | [[Category: Hormone]] |
| - | [[Category: | + | [[Category: Human insulin]] |
| - | [[Category: | + | [[Category: Mutant]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:15:43 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:15, 2 May 2008
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.
About this Structure
1K3M is a Protein complex structure. 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 Page seeded by OCA on Fri May 2 22:15:43 2008
Categories: Protein complex | Chu, Y C. | Hua, Q X. | Jia, W. | Katsoyannis, P G. | Nakagawa, S H. | Weiss, M A. | Xu, B. | Hormone | Human insulin | Mutant
