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• W2317019353 startingPage "3290" @default.
• W2317019353 abstract "Metallothioneins are a family of small, cysteine rich proteins that have been implicated in a range of roles including toxic metal detoxification, protection against oxidative stress, and as metallochaperones involved in the homeostasis of both essential zinc and copper. We report that human metallothionein 1a, well-known to coordinate 7 Zn2+ or Cd2+ ions with 20 cysteinyl thiols, will bind 8 structurally significant Cd2+ ions, leading to the formation of the supermetalated Cd8-βα-rhMT 1a species, for which the structure is a novel single domain. ESI–mass spectrometry was used to determine the exact metalation status of the βα-rhMT. The derivative-shaped CD envelope of Cd7-βα-rhMT [peak extrema (+) 260 and (−) 239 nm] changed drastically upon formation of the Cd8-βα-rhMT with the appearance of a sharp monophasic CD band centered on 252 nm, a feature indicative of the loss of cluster symmetry. The structural significance of the eighth Cd2+ ion was determined from a combination of direct and indirect 113Cd nuclear magnetic resonance (NMR) spectra. In the case of Cd8-βα-rhMT, only four peaks were observed in the direct 113Cd NMR spectrum. Significantly, while both of the isolated domains can be supermetalated forming Cd4-β-rhMT and Cd5-α-rhMT, Cd8-βα-rhMT and not Cd9-βα-rhMT was observed following addition of excess Cd2+. We propose that both domains act in concert to coordinate the eighth Cd2+ atom, and furthermore that this interaction results in a coalescence of the two domains leading to collapse of the two-domain structure. This is the first report of a possible single-“superdomain” metallothionein structure for Zn2+ and Cd2+ binding mammalian proteins. A computational model of a possible single-domain structure of Cd8-βα-rhMT is described." @default.
• W2317019353 created "2016-06-24" @default.
• W2317019353 creator A5009418462 @default.
• W2317019353 creator A5009769045 @default.
• W2317019353 creator A5034517384 @default.
• W2317019353 date "2012-02-06" @default.
• W2317019353 modified "2023-10-13" @default.
• W2317019353 title "Single Domain Metallothioneins: Supermetalation of Human MT 1a" @default.
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• W2317019353 doi "https://doi.org/10.1021/ja211767m" @default.
• W2317019353 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22242602" @default.
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