Abstract
Metallothioneins (MTs) are low-molecular-mass cysteine-rich proteins with the ability to bind mono- and divalent metal ions with the electron configuration d 10 in form of metal-thiolate clusters. MTs are thought, among others, to play a role in the homeostasis of essential Zn(II) and Cu(I) ions. Besides these metal ions also Cd(II) can be bound to certain MTs in vivo, giving rise to the perception that another physiological role of MTs is in the detoxification of heavy metal ions. Substitution of the spectroscopically silent Zn(II) ions in metalloproteins by Cd(II) proved to be an indispensable tool to probe the Zn(II) sites in vitro. In this review, methods applied in the studies of structural and chemical properties of Cd-MTs are presented. The first section focuses on the physical basis of spectroscopic techniques such as electronic absorption, circular dichroism (CD), magnetic CD, X-ray absorption, and perturbed angular correlation of γ-rays spectroscopy, as well as mass spectrometry, and their applications to Cd-MTs from different organisms. The following is devoted to the discussion of metal binding affinities of Cd-MTs, cluster dynamics, the reactivity of bound Cd(II) ions with metal ion chelators and of thiolate ligands with alkylating and oxidizing agents. Finally, a brief summary of the known three-dimensional structures of Cd-MTs, determined almost exclusively by multinuclear NMR techniques, is presented. Besides Cd-MTs, the described methods can also be applied to the study of metal binding sites in other metalloproteins.
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Abbreviations
- 5F-BAPTA:
-
1,2 -bis-(2-amino-5-fluorophenoxy)ethane-N, N, N’,N’-tetraacetic acid
- CD:
-
circular dichroism
- COSY:
-
correlation spectroscopy
- CTTS:
-
charge-transfer-to-solvent
- Cys:
-
cysteine
- DTNB:
-
5,5’-dithiobis-(2-nitrobenzoic acid)
- EDTA:
-
ethylenediamine-N,N,N’,N’-tetraacetate
- EPR:
-
electron spin resonance
- ESI:
-
electrospray ionization
- EXAFS:
-
extended X-ray absorption fine structure
- FT-IR:
-
Fourier transform infrared (spectroscopy)
- GIF:
-
growth inhibitory factor
- GST:
-
glutathione-S-transferase
- His:
-
histidine
- HSQC:
-
heteronuclear single quantum coherence
- LLCT:
-
ligand-to-ligand charge-transfer
- LMCT:
-
ligand-to-metal charge-transfer
- LUMO:
-
lowest unoccupied molecular orbital
- MALDI:
-
matrix assisted laser desorption ionisation
- MCD:
-
magnetic circular dichroism
- MD:
-
molecular dynamics
- MM:
-
molecular mechanics
- MO:
-
molecular orbital
- MS:
-
mass spectrometry
- MT:
-
metallothionein
- NMR:
-
nuclear magnetic resonance
- NOE:
-
nuclear Overhauser effect
- NQI:
-
nuclear quadrupole interaction
- NTA:
-
nitrilotriacetate
- PAC:
-
perturbed angular correlation
- PDB:
-
Protein Data Bank
- RMSD:
-
root-mean-square deviation
- XANES:
-
X-ray absorption near-edge structure
- XAS:
-
X-ray absorption spectroscopy
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Financial support by the Swiss National Science Foundation (SNSF Professorship PP002-119106/1 to E.F.) is gratefully acknowledged.
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Freisinger, E., Vašák, M. (2013). Cadmium in Metallothioneins. In: Sigel, A., Sigel, H., Sigel, R. (eds) Cadmium: From Toxicity to Essentiality. Metal Ions in Life Sciences, vol 11. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5179-8_11
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