1kmf

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[[Image:1kmf.gif|left|200px]]
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{{Seed}}
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[[Image:1kmf.png|left|200px]]
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{{STRUCTURE_1kmf| PDB=1kmf | SCENE= }}
{{STRUCTURE_1kmf| PDB=1kmf | SCENE= }}
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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'''
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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===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 11866509 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11866509}}
==About this Structure==
==About this Structure==
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1KMF is a [[Protein complex]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMF OCA].
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1KMF is a [[Protein complex]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMF 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 22:54:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 10:33:17 2008''

Revision as of 07:33, 2 July 2008

Image:1kmf.png

Template:STRUCTURE 1kmf

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

Template:ABSTRACT PUBMED 11866509

About this Structure

1KMF is a Protein complex structure. Full experimental 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 Wed Jul 2 10:33:17 2008

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