1a7f
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(New page: 200px<br /> <applet load="1a7f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a7f" /> '''INSULIN MUTANT B16 GLU, B24 GLY, DES-B30, N...)
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Revision as of 13:50, 12 November 2007
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INSULIN MUTANT B16 GLU, B24 GLY, DES-B30, NMR, 20 STRUCTURES
Contents |
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.
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
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
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