Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer. / Huus, Kasper; Havelund, Svend; Olsen, Helle B; Sigurskjold, Bent W; van de Weert, Marco; Frokjaer, Sven.

In: Biochemistry, Vol. 45, No. 12, 28.03.2006, p. 4014-4024.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Huus, K, Havelund, S, Olsen, HB, Sigurskjold, BW, van de Weert, M & Frokjaer, S 2006, 'Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer', Biochemistry, vol. 45, no. 12, pp. 4014-4024. https://doi.org/10.1021/bi0524520

APA

Huus, K., Havelund, S., Olsen, H. B., Sigurskjold, B. W., van de Weert, M., & Frokjaer, S. (2006). Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer. Biochemistry, 45(12), 4014-4024. https://doi.org/10.1021/bi0524520

Vancouver

Huus K, Havelund S, Olsen HB, Sigurskjold BW, van de Weert M, Frokjaer S. Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer. Biochemistry. 2006 Mar 28;45(12):4014-4024. https://doi.org/10.1021/bi0524520

Author

Huus, Kasper ; Havelund, Svend ; Olsen, Helle B ; Sigurskjold, Bent W ; van de Weert, Marco ; Frokjaer, Sven. / Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer. In: Biochemistry. 2006 ; Vol. 45, No. 12. pp. 4014-4024.

Bibtex

@article{52123bc06c3711dcbee902004c4f4f50,
title = "Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer",
abstract = "The influence of ligand binding and conformation state on the thermostability of hexameric zinc-insulin was studied by differential scanning calorimetry (DSC). The insulin hexamer exists in equilibrium between the forms T6, T3R3, and R6. Phenolic ligands induce and stabilize the T3R3- and R6-states which are further stabilized by binding of certain anions that do not stabilize the T6-state. It was shown that the thermostability of the resorcinol-stabilized R6-state was significantly higher than that of the T6-state. Further analysis showed that phenol- and m-cresol-stabilized R6-hexamer loses three ligands before reaching the unfolding temperature and hence unfolds from the T3R3-state. The relative affinity of the four tested anionic ligands was found, by DSC, to be thiocyanate = 4-hydroxy-3-nitrobenzoate p-aminobenzoate chloride. The results correlate with other methods and demonstrate that DSC provides a general and useful method of evaluation of both phenolic and anionic ligand binding to insulin without the use of probes or other alterations of the system of interest. However, it is a prerequisite that the binding is strong enough to saturate the binding sites at temperatures around the unfolding transition.",
keywords = "Allosteric Regulation, Biopolymers, Calorimetry, Differential Scanning, Humans, Insulin, Ligands, Phenols, Spectrophotometry, Ultraviolet, Zinc",
author = "Kasper Huus and Svend Havelund and Olsen, {Helle B} and Sigurskjold, {Bent W} and {van de Weert}, Marco and Sven Frokjaer",
year = "2006",
month = "3",
day = "28",
doi = "10.1021/bi0524520",
language = "English",
volume = "45",
pages = "4014--4024",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "12",

}

RIS

TY - JOUR

T1 - Ligand binding and thermostability of different allosteric states of the insulin zinc-hexamer

AU - Huus, Kasper

AU - Havelund, Svend

AU - Olsen, Helle B

AU - Sigurskjold, Bent W

AU - van de Weert, Marco

AU - Frokjaer, Sven

PY - 2006/3/28

Y1 - 2006/3/28

N2 - The influence of ligand binding and conformation state on the thermostability of hexameric zinc-insulin was studied by differential scanning calorimetry (DSC). The insulin hexamer exists in equilibrium between the forms T6, T3R3, and R6. Phenolic ligands induce and stabilize the T3R3- and R6-states which are further stabilized by binding of certain anions that do not stabilize the T6-state. It was shown that the thermostability of the resorcinol-stabilized R6-state was significantly higher than that of the T6-state. Further analysis showed that phenol- and m-cresol-stabilized R6-hexamer loses three ligands before reaching the unfolding temperature and hence unfolds from the T3R3-state. The relative affinity of the four tested anionic ligands was found, by DSC, to be thiocyanate = 4-hydroxy-3-nitrobenzoate p-aminobenzoate chloride. The results correlate with other methods and demonstrate that DSC provides a general and useful method of evaluation of both phenolic and anionic ligand binding to insulin without the use of probes or other alterations of the system of interest. However, it is a prerequisite that the binding is strong enough to saturate the binding sites at temperatures around the unfolding transition.

AB - The influence of ligand binding and conformation state on the thermostability of hexameric zinc-insulin was studied by differential scanning calorimetry (DSC). The insulin hexamer exists in equilibrium between the forms T6, T3R3, and R6. Phenolic ligands induce and stabilize the T3R3- and R6-states which are further stabilized by binding of certain anions that do not stabilize the T6-state. It was shown that the thermostability of the resorcinol-stabilized R6-state was significantly higher than that of the T6-state. Further analysis showed that phenol- and m-cresol-stabilized R6-hexamer loses three ligands before reaching the unfolding temperature and hence unfolds from the T3R3-state. The relative affinity of the four tested anionic ligands was found, by DSC, to be thiocyanate = 4-hydroxy-3-nitrobenzoate p-aminobenzoate chloride. The results correlate with other methods and demonstrate that DSC provides a general and useful method of evaluation of both phenolic and anionic ligand binding to insulin without the use of probes or other alterations of the system of interest. However, it is a prerequisite that the binding is strong enough to saturate the binding sites at temperatures around the unfolding transition.

KW - Allosteric Regulation

KW - Biopolymers

KW - Calorimetry, Differential Scanning

KW - Humans

KW - Insulin

KW - Ligands

KW - Phenols

KW - Spectrophotometry, Ultraviolet

KW - Zinc

U2 - 10.1021/bi0524520

DO - 10.1021/bi0524520

M3 - Journal article

C2 - 16548529

VL - 45

SP - 4014

EP - 4024

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 12

ER -

ID: 1100869