1kmf
From Proteopedia
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'''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALLO-ILE, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES''' | '''NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALLO-ILE, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES''' | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KMF is a [[Protein complex]] structure | + | 1KMF is a [[Protein complex]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMF 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 22:54:49 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:54, 2 May 2008
NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALLO-ILE, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES
Overview
The hydrophobic core of vertebrate insulins contains an invariant isoleucine residue at position A2. Lack of variation may reflect this side-chain's dual contribution to structure and function: Ile(A2) is proposed both to stabilize the A1-A8 alpha-helix and to contribute to a "hidden" functional surface exposed on receptor binding. Substitution of Ile(A2) by alanine results in segmental unfolding of the A1-A8 alpha-helix, lower thermodynamic stability and impaired receptor binding. Such a spectrum of perturbations, although of biophysical interest, confounds interpretation of structure-activity relationships. To investigate the specific contribution of Ile(A2) to insulin's functional surface, we have employed non-standard mutagenesis: inversion of side-chain chirality in engineered monomer allo-Ile(A2)-DKP-insulin. Although the analogue retains native structure and stability, its affinity for the insulin receptor is impaired by 50-fold. Thus, whereas insulin's core readily accommodates allo-isoleucine at A2, its activity is exquisitely sensitive to chiral inversion. We propose that the Ile(A2) side-chain inserts within a chiral pocket of the receptor as part of insulin's hidden functional surface.
About this Structure
1KMF is a Protein complex structure. Full crystallographic information is available from OCA.
Reference
Chiral mutagenesis of insulin's hidden receptor-binding surface: structure of an allo-isoleucine(A2) analogue., Xu B, Hua QX, Nakagawa SH, Jia W, Chu YC, Katsoyannis PG, Weiss MA, J Mol Biol. 2002 Feb 22;316(3):435-41. PMID:11866509 Page seeded by OCA on Fri May 2 22:54:49 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
