Copper pumping ATPases: common concepts in bacteria and

Recently, four genes encoding putative copper pumping ATPases have been cloned from widely different sources: two genes from Enterococcus hirae that are involved in copper metabolism and two human genes that are defective in the copper-related Wilson and Menkes disease. The predicted gene products are P-type ATPases. They exhibit extensive sequence similarity and appear to be members of a new class of ATP driven copper pumps involved in the regulation of cellular copper. Key worak: Conner; ATPase; Transport; Menkes disease; Wilson disease; Enterococcus hirae 1. Copper is a toxic but essential element Copper functions as cofactor in various redox en-zymes such as lysyl oxidase, cytochrome c oxidase, su-peroxide dismutase, dopamine B-hydroxylase, and ty-rosinase. Copper is also a component of bacterial azurins and plastocyanins. At the same time, copper is very toxic to both eukaryotic and prokaryotic cells. Copper ions can bind to proteins and nucleic acids and can cause the oxidation of lipids and proteins. The formation of delete-rious free radicals is also enhanced by copper ions. In-deed, this toxicity is put to use in disease prevention in vegetable cultures. For cell viability, regulation of intra-cellular copper activity is thus crucially important and mechanisms must exist for the homeostasis of copper. Recent studies of copper resistance in the Gram-posi-tive bacterium Enterococcus hirae has led to the discov-ery of two putative copper transporting ATPases. Inter-estingly, these enzymes exhibit extensive sequence identity to two human ATPases that are defective in the copper-related Menkes and Wilson disease. Copper ho-meostasis has also been extensively studied in other bac-teria, notably Escherichia coli and Pseudomonas syrin-gae. However, there is at present no evidence for ATP driven copper transport in these organisms and they will not be considered here. 2. Genes of copper metabolism in Enterococcus hirae In Enterococcus hirae, an operon involved in coppe