TAILIEUCHUNG - Báo cáo khoa học: Neuronal growth-inhibitory factor (metallothionein-3): a unique metalloprotein

Metallothionein (MT) was first identified in 1957 by M. Margosch and B. Vallee as ‘a cadmium protein from equine kidney cortex’. In fact, the small protein was a Cu, Zn-containing protein, with an array of con-served cysteine residues. | ỊFEBS Journal MINIREVIEW SERIES Neuronal growth-inhibitory factor metallothionein-3 a unique metalloprotein Zhong-Xian Huang ChemicalBiology Laboratory Chemistry Department Fudan University Shanghai China Metallothionein MT was first identified in 1957 by M. Margosch and B. Vallee as a cadmium protein from equine kidney cortex . In fact the small protein was a Cu Zn-containing protein with an array of conserved cysteine residues. Since its discovery intensive study has been focused on this protein but its functions remain elusive. In 1991 a new small protein which exhibited neuronal growth-inhibitory activity was isolated by Y. Ush-ida et al. from healthy human brain this protein was subsequently named neuronal growth-inhibitory factor GIF . It was later found that this protein showed high sequence similarity 70 to MT together with conserved cysteines and metal content and it was renamed MT3. The neuronal growth-inhibitory activity of this protein is unique among members of the MT family. In their paper Ushida et al. wrote that . we do not know the mechanism of growth inhibitory action of GIF especially why GIF but not MT has growth inhibitory activity despite their homologous sequences. To answer this question we have been carrying out a study of structure-property-reactivity-function relationships. Owing to the conformational flexibility of its polypeptide chain there is no GIF crystal structure available as yet. The solution structure of the a-domain of rat and human Cd-GIF has been determined by means of NMR spectroscopy but the structure of the b-domain could not be solved because of insufficient NOE connectivities. However a model of the b-domain structure of GIF was constructed on the basis of molecular dynamic simulation and a systematical mutagenesis study has been performed. This has revealed that the particular conformation of TCPCP 5-9 in the b-domain the exposure of the metal-thiolate clusters the dynamics of EAAEAE 55-60 in the a-domain and the .

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