1H n.m.r. studies of insulin

Ramesh, Vasudevan; Bradbury, J. H.

doi:10.1111/j.1399-3011.1986.tb03241.x

Cited by 15 publications

References 19 publications

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Binding of phenol to R6 insulin hexamers*

Berchtold¹,

Hilgenfeld²

1999

Biopolymers

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Small amounts of phenolic compounds are being used as preservatives in pharmaceutical insulin preparations. It has been shown previously that these compounds bind to specific sites on the insulin hexamer and act as allosteric effectors, inducing a transformation of the T6 hexamer to the R6 hexamer, via a T3R3 intermediate. In this article, the crystal structures of eight different insulin derivatives, all in the phenol‐containing R6 form, are analyzed with respect to their phenol‐binding sites. While six phenol molecules are normally bound per insulin hexamer, one of the engineered insulins appears to contain only three phenols but yet exists in an R6 conformation. This observation provides additional evidence for an inherent nonequivalence of the two trimers in the insulin hexamer. The unusual observation of a seventh phenol molecule bound to the hexamer of crystalline A21Gly–B31,B32Arg2 insulin (HOE 901), a long‐acting derivative currently undergoing phase III clinical trials, provides a partial explanation for its protracted activity. © 1999 John Wiley & Sons, Inc. Biopoly 51: 165–172, 1999

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Binding of phenol to R6 insulin hexamers*

Berchtold¹,

Hilgenfeld²

1999

Biopolymers

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Changes in secondary structure follow the dissociation of human insulin hexamers: A circular dichroism study

Melberg

Johnson

1990

Proteins

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Vacuum UV circular dichroism spectra measured down to 178 nm for hexameric 2-zinc human insulin, zinc-free human insulin, and the two engineered and biologically active monomeric mutants, [B/S9D] and [B/S9D,T27E] human insulin, show significant differences. The secondary structure analysis of the 2-zinc human insulin (T6) in neutral solution was determined: 57% helix, 1% beta-strand, 18% turn, and 24% random coil. This is very close to the corresponding crystal structure showing that the solution and solid structures are similar. The secondary structure of the monomer shows a 10-15% increase in antiparallel beta-structure and a corresponding reduction in random coil structure. These structural changes are consistent with an independent analysis of the corresponding difference spectra. The advantage of secondary structure analyses of difference spectra is that the contribution of odd spectral features stemming mainly from side chain chromophores is minimized and the sensitivity of the analyses improved. Analysis of the CD spectra of T6 2-zinc, zinc-free human insulin and monomeric mutant insulin by singular value decomposition indicates that the secondary structure changes following the dissociation of hexamers into dimers and monomers are two-state processes.

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T-R Transition

Wollmer¹

2002

Insulin &Amp; Related Proteins - Structure to Function and Pharmacology

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1H n.m.r. studies of insulin

Cited by 15 publications

References 19 publications

Binding of phenol to R6 insulin hexamers*

Binding of phenol to R6 insulin hexamers*

Changes in secondary structure follow the dissociation of human insulin hexamers: A circular dichroism study

T-R Transition

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