Clioquinol (CQ), a once popular antibiotic, was used to inhibit the growth of microorganisms. Recently, CQ and its analog PBT2 have shown encouraging effects in the animal and clinical trials for Alzheimer's disease (AD). However, the mechanism by which this class of molecules works remains controversial. In this work, we used the yeast Saccharomyces cerevisiae as a model to study how CQ affect...

Accumulating evidence suggests that hepcidin, a 25-residue peptide hormone, is the master regulator of iron metabolism. Further evidence suggests that the five N-terminal amino acids are crucial for mediating its biological function. With a histidine residue at position 3, this region also has the potential to bind bivalent metal ions. To characterize this hepcidin-metal interaction in detail, ...

The basic amino acid histidine inhibited yeast cell growth more severely than lysine and arginine. Overexpression of CTR1, which encodes a high-affinity copper transporter on the plasma membrane, or addition of copper to the medium alleviated this cytotoxicity. However, the intracellular level of copper ions was not decreased in the presence of excess histidine. These results indicate that hist...

The copper resistance determinant copARZ, which encodes a CPx-type copper ATPase efflux protein, a transcriptional regulator, and a putative intracellular copper chaperone, was functionally characterized for the phytopathogenic bacterium Agrobacterium tumefaciens. These genes are transcribed as an operon, and their expression is induced in response to increasing copper and silver ion concentrat...

The presence of the copper ion at the active site of human wild type copper-zinc superoxide dismutase (CuZnSOD) is essential to its ability to catalyze the disproportionation of superoxide into dioxygen and hydrogen peroxide. Wild type CuZnSOD and several of the mutants associated with familial amyotrophic lateral sclerosis (FALS) (Ala(4) --> Val, Gly(93) --> Ala, and Leu(38) --> Val) were expr...

Malaria is one of the world's most devastating diseases, particularly in the tropics. In humans, Plasmodium falciparum lives mainly within red blood cells, and malaria pathogenesis depends on the red blood cells being infected with the parasite. Nonesterified fatty acids (NEFAs), including cis-9-octadecenoic acid, and phospholipids have been critical for complete parasite growth in serum-free c...

Copper ATPases, in analogy with other members of the P-ATPase superfamily, contain a catalytic headpiece including an aspartate residue reacting with ATP to form a phosphoenzyme intermediate, and transmembrane helices containing cation-binding sites [TMBS (transmembrane metal-binding sites)] for catalytic activation and cation translocation. Following phosphoenzyme formation by utilization of A...

The role of plasmalogen phospholipids for copper-induced lipid oxidation was evaluated. Using 1H-NMR we observed that the copper (CuSO4)-promoted oxidative degradation of polyunsaturated fatty acids in micellar solution was dose-dependently attenuated by the plasmalogen lysoplasmenylethanolamine from bovine brain (lysoBP-PtdEtn). This was due to a direct interaction of copper ions with the plas...

The stoichiometries and the affinity toward simple and paired metal ions of synthetic amyloid-beta(1-40) peptide (Abeta1-40) were investigated by electrospray ion trap mass spectrometry (ESI-MS), circular dichroism (CD), and atomic force microscopy (AFM). The results lead to the working hypothesis that pH-dependent metal binding to Abeta1-40 may induce conformational changes, which affect the a...

When Neurospora crassa is grown in the presence of Cu(II) ions, it accumulates the metal with the concomitant synthesis of a low molecular weight copper-binding protein. The molecule binds 6 g-atom of copper per mole protein (Mr = 2200) and shows a striking sequence homology to the zinc- and cadmium-binding vertebrate metallothioneins. Absorption, circular dichroism, and electron paramagnetic r...