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To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by… (More)
We found that cyt c Y67H and Y67R variants represent a state which resembles the conformational intermediate state in cyt c with high peroxidase activity; and also the hydrogen bond network around Tyr67 is associated with the conformational transition of cyt c; these suggest that the hydrogen bond network around Tyr67 is essential in maintaining the cyt c… (More)
Aggregation and cytotoxicity of Aβ with redox-active metals in neuronal cells have been implicated in the progression of Alzheimer disease. Human metallothionein (MT) 3 is highly expressed in the normal human brain and is downregulated in Alzheimer disease. Zn7MT3 can protect against the neuronal toxicity of Aβ by preventing copper-mediated Aβ aggregation,… (More)
We demonstrate for the first time that cytochrome c undergoes a distinct pathway in the alkaline conformational transition from its pro-apoptotic conformational transition, which may have important functional consequences in vivo.
Alzheimer's disease is characterized by progressive loss of neurons accompanied by the formation of intraneural neurofibrillary tangles and extracellular amyloid plaques. Human neuronal growth inhibitory factor, classified as metallothionein-3 (MT-3), was found to be related to the neurotrophic activity promoting cortical neuron survival and dendrite… (More)
The continued interest in protein engineering has led to intense efforts in developing novel stable enzymes, which could not only give boost to industrial and biomedical applications, but also enhance our understanding of the structure-function relationships of proteins. We present here the generation of three hybrid proteins of cytochrome c (cyt c) and… (More)
Neuronal growth inhibitory factor (GIF), also known as metallothionein (metallothionein-3), impairs the survival and neurite formation of cultured neurons. It is known that the α-β domain-domain interaction of hGIF is crucial to the neuron growth inhibitory bioactivity although the exact mechanism is not clear. Herein, the β(MT3)-β(MT3) mutant and the… (More)
The catalytic activity of cytochrome c (cyt c) to peroxidize cardiolipin to its oxidized form is required for the release of pro-apoptotic factors from mitochondria, and for execution of the subsequent apoptotic steps. However, the structural basis for this peroxidation reaction remains unclear. In this paper, we determined the three-dimensional NMR… (More)
Neuronal growth inhibitory factor (GIF), also known as metallothionein (metallothionein-3), impairs the survival and neurite formation of cultured neurons. It is known that the alpha-beta domain-domain interaction of hGIF is crucial to the neuron growth inhibitory bioactivity although the exact mechanism is not clear. Herein, the beta(MT3)-beta(MT3) mutant… (More)
Truncated acetyl-coenzyme A synthase (ACS) was successfully converted into functional nickel superoxide dismutase (Ni-SOD) by molecular design and the designed metalloproteins possess new spectroscopic, structural, and electrochemical characteristics required for catalyzing O(2)(˙-) disproportionation, and exhibit impressive Ni-SOD activity.