Enhancing the T R Transition of Insulin by Helix-Promoting Sequence Modifications at the N-Terminal B-Chain
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Jewad Shneine
Abstract
Structurally, the T→R transition of insulin mainly consists of a rearrangement of the N-terminal B-chain (residues B1–B8) from extended to helical in one or both of the trimers of the hexamer. The dependence of the transition on the nature of the ligands inducing it, such as inorganic anions or phenolic compounds, as well as of the metal ions complexing the hexamer, has been the subject of extensive investigations. This study explores the effect of helix-enhancing modifications of the N-terminal B-chain sequence where the transition actually occurs, with special emphasis on N-capping. In total 15 different analogues were prepared by semisynthesis. 80% of the hexamers of the most successful analogues with zinc were found to adopt the T3R3 state in the absence of any transforming ligands, as compared to only 4% of wild-type insulin. Transformation with SCN− ions can exceed the T3R3 state where it stops in the case of wild-type insulin. Full transformation to the R6 state can be achieved by only one-tenth the phenol concentration required for wild-type insulin, i. e. almost at the stoichiometric ratio of 6 phenols per hexamer.
Copyright © 2000 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- The Twin-Arginine Translocation System: A Novel Means of Transporting Folded Proteins in Chloroplasts and Bacteria
- De Novo DNA Methylation at Nonrandom Founder Sites 5' from an Unmethylated Minimal Origin of DNA Replication in Latent Epstein-Barr Virus Genomes
- Trichostatin A Modulates Expression of p21waf1/cip1, Bcl-xL, ID1, ID2, ID3, CRAB2, GATA-2, hsp86 and TFIID/TAFII31 mRNA in Human Lung Adenocarcinoma Cells
- Effects of the Active Aldehyde Group Generated by RNA N-Glycosidase in the Sarcin/Ricin Domain of Rat 28S Ribosomal RNA on Peptide Elongation
- Responses to Peroxynitrite in Yeast: Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) as a Sensitive Intracellular Target for Nitration and Enhancement of Chaperone Expression and Ubiquitination
- Enhancing the T R Transition of Insulin by Helix-Promoting Sequence Modifications at the N-Terminal B-Chain
- Structure-Dependent Effects of Glucose-Containing Analogs of Platelet Activating Factor (PAF) on Membrane Integrity
- Two Different Mechanisms for Activation of Cyclic PIP Synthase: by a G Protein or by Protein Tyrosine Phosphorylation
- 3-Hydroxybenzoate:Coenzyme A Ligase from Cell Cultures of Centaurium erythraea: Isolation and Characterization
- Gel Chromatographic Characterization of the Hydrophobic Interaction of Glycosylphosphatidylinositol-Alkaline Phosphatase with Detergents
- Immunolabeling of CD3-Positive Lymphocytes with a Recombinant Single-Chain Antibody/Alkaline Phosphatase Conjugate
- Phage Display of RNase A and an Improved Method for Purification of Phages Displaying RNases
