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The effect of nitric oxide on metal release from metallothionein-3: gradual unfolding of the protein

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Abstract

Metallothionein-3 (MT-3), or neuronal growth inhibitory factor, which exhibits growth inhibitory activity, is a brain-specific metallothionein. In this study, the effect of nitric oxide (NO) on metal release (using Cd2+ as a probe) from MT-3 was examined by 113Cd and 2D [1H–15N] heteronuclear single-quantum coherence NMR spectroscopy. The exposure of human MT-3 to NO leads to a nonselective release of the three metals from the β-domain. In contrast to metallothionein-1 and metallothionein-2, two of the bound metals in the α-domain were also partially released, with the domain structure remaining almost unchanged. Further addition of NO resulted in the complete release of metals and concomitant unfolding of the protein. The preference of release of the two metals in the α-domain was attributed to the presence of two slightly different coordination environments for the four cadmium/zinc atoms.

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Abbreviations

AD:

Alzheimer’s disease

CA:

Cornu ammonis

DEA/NO:

1,1-Diethyl-2-hydroxy-2-nitrosohydrazine

DTT:

1,4-Dithiothreitol

GIF:

Growth inhibitory factor

GST:

Gluathione S-transferase

hMT-3:

Human metallothionein-3

HSQC:

Heteronuclear single-quantum coherence

ICP-MS:

Inductively coupled plasma mass spectrometry

MT:

Metallothionein

NOE:

Nuclear Overhauser effect

NOESY:

Nuclear Overhauser enhancement spectroscopy

Tris:

Tris(hydroxymethyl)aminomethane

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Acknowledgements

This work was supported by NSFC/RGC (to H.S.), National Science Foundation of China (to Z.X.H. and to H.S. for an Outstanding Young Scholar Award), the Area of Excellence (AoE) of the University Grants Committee of Hong Kong and the University of Hong Kong. We are grateful for an equipment grant (UDF) from the University of Hong Kong for the 600 MHz NMR facility.

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Authors and Affiliations

  1. Department of Chemistry and Open Laboratory of Chemical Biology, The University of Hong Kong, Pokfulam, Hong Kong, People’s Republic of China

    Hui Wang, Hongyan Li & Hongzhe Sun

  2. Chemical Biology Laboratory, Department of Chemistry, Fudan University, Shanghai, 200433, People’s Republic of China

    Bin Cai & Zhong-Xian Huang

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  1. Hui Wang
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  2. Hongyan Li
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  3. Bin Cai
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Correspondence to Zhong-Xian Huang or Hongzhe Sun.

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Wang, H., Li, H., Cai, B. et al. The effect of nitric oxide on metal release from metallothionein-3: gradual unfolding of the protein. J Biol Inorg Chem 13, 411–419 (2008). https://doi.org/10.1007/s00775-007-0331-x

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  • DOI: https://doi.org/10.1007/s00775-007-0331-x

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