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Artur Krężel, Wolfgang Maret
The functions, purposes, and roles of metallothioneins have been the subject of speculations since the discovery of the protein over 60 years ago. This article guides through the history of investigations and resolves multiple contentions by providing new interpretations of the structure-stability-function relationship. It challenges the dogma that the biologically relevant structure of the mammalian proteins is only the one determined by X-ray diffraction and NMR spectroscopy. The terms metallothionein and thionein are ambiguous and insufficient to understand biological function. The proteins need to be seen in their biological context, which limits and defines the chemistry possible. They exist in multiple forms with different degrees of metalation and types of metal ions. The homoleptic thiolate coordination of mammalian metallothioneins is important for their molecular mechanism. It endows the proteins with redox activity and a specific pH dependence of their metal affinities. The proteins, therefore, also exist in different redox states of the sulfur donor ligands. Their coordination dynamics allows a vast conformational landscape for interactions with other proteins and ligands. Many fundamental signal transduction pathways regulate the expression of the dozen of human metallothionein genes. Recent advances in understanding the control of cellular zinc and copper homeostasis are the foundation for suggesting that mammalian metallothioneins provide a highly dynamic, regulated, and uniquely biological metal buffer to control the availability, fluctuations, and signaling transients of the most competitive Zn(II) and Cu(I) ions in cellular space and time.
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Krężel, A., & Maret, W. (2021). The Bioinorganic Chemistry of Mammalian Metallothioneins. Chemical Reviews, 121(23), 14594–14648. https://doi.org/10.1021/acs.chemrev.1c00371
Krężel, Artur, and Wolfgang Maret. "The Bioinorganic Chemistry of Mammalian Metallothioneins." Chemical Reviews, vol. 121, no. 23, 2021, pp. 14594–14648, https://doi.org/10.1021/acs.chemrev.1c00371.
Krężel, Artur, and Wolfgang Maret. "The Bioinorganic Chemistry of Mammalian Metallothioneins." Chemical Reviews 121, no. 23 (2021): 14594–14648. https://doi.org/10.1021/acs.chemrev.1c00371.
Krężel A., Maret W. The Bioinorganic Chemistry of Mammalian Metallothioneins // Chemical Reviews. — 2021. — Vol. 121, № 23. — P. 14594–14648. — URL: https://doi.org/10.1021/acs.chemrev.1c00371
@article{krezel2021bioinorganic,
title = {{The Bioinorganic Chemistry of Mammalian Metallothioneins}},
author = {Artur Krężel and Wolfgang Maret},
journal = {Chemical Reviews},
year = {2021},
volume = {121},
number = {23},
pages = {14594--14648},
doi = {10.1021/acs.chemrev.1c00371},
url = {https://doi.org/10.1021/acs.chemrev.1c00371}
}TY - JOUR AU - Krężel, Artur AU - Maret, Wolfgang TI - The Bioinorganic Chemistry of Mammalian Metallothioneins JO - Chemical Reviews VL - 121 IS - 23 SP - 14594 EP - 14648 PY - 2021 DA - 2021/10/15 DO - 10.1021/acs.chemrev.1c00371 UR - https://doi.org/10.1021/acs.chemrev.1c00371 ER -
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