1a7f
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1a7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a7f OCA], [http://www.ebi.ac.uk/pdbsum/1a7f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1a7f RCSB]</span> | ||
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==Overview== | ==Overview== | ||
Despite years of effort to clarify the structural basis of insulin receptor binding no clear consensus has emerged. It is generally believed that insulin receptor binding is accompanied by some degree of conformational change in the carboxy-terminal of the insulin B-chain. In particular, while most substitutions for PheB24 lead to inactive species, glycine or D-amino acids are well tolerated in this position. Here we assess the conformation change by solving the solution structure of the biologically active (GluB16, GlyB24, desB30)-insulin mutant. The structure in aqueous solution at pH 8 reveals a subtle, albeit well-defined rearrangement of the C-terminal decapeptide involving a perturbation of the B20-23 turn, which allows the PheB25 residue to occupy the position normally taken up by PheB24 in native insulin. The new protein surface exposed rationalizes the receptor binding properties of a series of insulin analogs. We suggest that the structural switch is forced by the structure of the underlying core of species invariant residues and that an analogous rearrangement of the C-terminal of the B-chain occurs in native insulin on binding to its receptor. | Despite years of effort to clarify the structural basis of insulin receptor binding no clear consensus has emerged. It is generally believed that insulin receptor binding is accompanied by some degree of conformational change in the carboxy-terminal of the insulin B-chain. In particular, while most substitutions for PheB24 lead to inactive species, glycine or D-amino acids are well tolerated in this position. Here we assess the conformation change by solving the solution structure of the biologically active (GluB16, GlyB24, desB30)-insulin mutant. The structure in aqueous solution at pH 8 reveals a subtle, albeit well-defined rearrangement of the C-terminal decapeptide involving a perturbation of the B20-23 turn, which allows the PheB25 residue to occupy the position normally taken up by PheB24 in native insulin. The new protein surface exposed rationalizes the receptor binding properties of a series of insulin analogs. We suggest that the structural switch is forced by the structure of the underlying core of species invariant residues and that an analogous rearrangement of the C-terminal of the B-chain occurs in native insulin on binding to its receptor. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], Hyperproinsulinemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]], MODY, one form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176730 176730]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: neutral ph]] | [[Category: neutral ph]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:34:53 2008'' |
Revision as of 15:34, 30 March 2008
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
INSULIN MUTANT B16 GLU, B24 GLY, DES-B30, NMR, 20 STRUCTURES
Overview
Despite years of effort to clarify the structural basis of insulin receptor binding no clear consensus has emerged. It is generally believed that insulin receptor binding is accompanied by some degree of conformational change in the carboxy-terminal of the insulin B-chain. In particular, while most substitutions for PheB24 lead to inactive species, glycine or D-amino acids are well tolerated in this position. Here we assess the conformation change by solving the solution structure of the biologically active (GluB16, GlyB24, desB30)-insulin mutant. The structure in aqueous solution at pH 8 reveals a subtle, albeit well-defined rearrangement of the C-terminal decapeptide involving a perturbation of the B20-23 turn, which allows the PheB25 residue to occupy the position normally taken up by PheB24 in native insulin. The new protein surface exposed rationalizes the receptor binding properties of a series of insulin analogs. We suggest that the structural switch is forced by the structure of the underlying core of species invariant residues and that an analogous rearrangement of the C-terminal of the B-chain occurs in native insulin on binding to its receptor.
About this Structure
1A7F is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A structural switch in a mutant insulin exposes key residues for receptor binding., Ludvigsen S, Olsen HB, Kaarsholm NC, J Mol Biol. 1998 May 29;279(1):1-7. PMID:9636695
Page seeded by OCA on Sun Mar 30 18:34:53 2008
