Structural Analyses of the Multicopper Site of CopG Support a Role as a Redox Enzyme

Abstract

Metal ions can be both essential components of cells as well as potential toxins if present in excess. Organisms utilize a variety of protein systems to maintain the concentration of metal ions within the appropriate range for cellular function, and to avoid concentrations where cellular damage can occur. In bacteria, numerous proteins contribute to copper homeostasis, including copper transporters, chelators, and redox enzymes. The genes that encode these proteins are often found in clusters, thus providing modular components that work together to achieve homeostasis. A better understanding of how these components function and cooperate to achieve metal ion resistance is needed, given the extensive use of metal ions, including copper, as broad-spectrum biocides in a variety of clinical and environmental settings. The copG gene is a common component of such copper resistance clusters, but its contribution to copper resistance is not well understood. In this review the available information about the CopG protein encoded by this gene is summarized. Comparison of the recent structure to diverse copper-containing metallochaperones, metalloenzymes, and electron transfer proteins suggests that CopG is a redox enzyme that uses multiple copper ions as active site redox cofactors to act on additional copper ion substrates. Mechanisms for both oxidase and reductase activity are proposed, and the biological advantages that these activities can contribute in conjunction with existing systems are described.