TAILIEUCHUNG - Báo cáo khoa học: Metal exchange in metallothioneins – a novel structurally significant Cd5 species in the alpha domain of human metallothionein 1a

Metallothioneins (MTs) are cysteine-rich, metal-binding proteins known to provide protection against cadmium toxicity in mammals. Metal exchange of Zn 2+ ions for Cd 2+ ions in metallothioneins is a critical process for which no mechanistic or structural information is currently available. | ỊFEBS Journal Metal exchange in metallothioneins - a novel structurally significant Cd5 species in the alpha domain of human metallothionein 1a Kelly E. Rigby Duncan Christopher W. Kirby and Martin J. Stillman Department of Chemistry The University of Western Ontario London Canada Keywords 113Cd NMR spectroscopy circular dichroism spectroscopy ESI mass spectrometry metal exchange metallothionein Correspondence M. J. Stillman Department of Chemistry Chemistry Building The University of Western Ontario London ON Canada N6A 5B7 Fax 1 519 661 3022 Tel 1 519 661 3821 E-mail Website http chem Received 7 January 2008 revised 27 February 2008 accepted 4 March 2008 doi Metallothioneins MTs are cysteine-rich metal-binding proteins known to provide protection against cadmium toxicity in mammals. Metal exchange of Zn2 ions for Cd2 ions in metallothioneins is a critical process for which no mechanistic or structural information is currently available. The recombinant human a domain of metallothionein isoform 1a which encompasses the metal-binding cysteines between Cys33 and Cys60 of the a domain of native human metallothionein 1a was studied. Characteristically this fragment coordinates four Cd2 ions to the 11 cysteinyl sulfurs and is shown to bind an additional Cd2 ion to form a novel Cd5a-MT species. This species is proposed here to represent an intermediate in the metal-exchange mechanism. The ESI mass spectrum shows the appearance of charge state peaks corresponding to a Cd5a species following addition of molar equivalents of Cd2 to a solution of Cd4a-MT. Significantly the structurally sensitive CD spectrum shows a sharp monophasic peak at 254 nm for the Cd5a species in contrast to the derivative-shaped spectrum of the Cd4a-MT species with peak maxima at 260 nm and 240 nm - indicating Cd-induced disruption of the exciton coupling between the original four Cd2 ions in the Cd4a species. The 113Cd chemical

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• genetics
• Structural biochemistry
• Structural Biology
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine