Archaeoglobus fulgidus CopB Is a Thermophilic Cu2+-ATPase

Abstract

Heavy metal transport ATPases, also called CPX-ATPases, belong to the P 1B

A Novel Regulatory Metal Binding Domain Is Present in the C Terminus of Arabidopsis Zn2+-ATPase HMA2

“…Moreover, it is reminiscent of the regulation by various N-and C-terminal cytoplasmic domains observed in many P 2 -type ATPases (57)(58)(59). Then, it can be postulated that C-MBDs control the enzyme rate-limiting step as shown for Cu ϩ and Cu 2ϩ -ATPases (32,33). Although this appears as a parsimonious mechanism, we cannot disregard that a non-rate-limiting step in the wild type enzyme becomes determinant of V max upon truncation of the C-MBD.…”

“…Analysis of their sequences reveals the presence of interesting C and N termini that might play regulatory roles as it is the case of N-MBDs in Cu ϩ -ATPases (15,27,32,33,56). In particular, the relatively long C termini have generated attention because they are uniquely associated to eukaryote Zn 2ϩ -ATPases (8,40,41).…”

“…In Cu ϩ -ATPases, N-MBDs receive the metal from specific Cu ϩ -chaperones (20 -26). Removal of the N-MBDs metal binding capability by truncation or mutation leads to reduced enzyme activity with small or no changes in metal affinity (27)(28)(29)(30)(31)(32)(33). Lutsenko and co-workers (34) have shown the Cu ϩ -dependent interaction of Wilson's disease protein N-MBDs with the large ATP binding cytoplasmic loop.…”

“…Lutsenko and co-workers (34) have shown the Cu ϩ -dependent interaction of Wilson's disease protein N-MBDs with the large ATP binding cytoplasmic loop. In our laboratory, we have observed that N-MBDs of Archaeoglobus fulgidus CopA, a Cu ϩ -ATPase, and CopB, a Cu 2ϩ -ATPase with a His-rich N-MBD, control the turnover rate of these enzymes but do not affect metal binding to the transport site (32,33). Specifically, the rate-limiting conformational change associated with metal release/dephosphorylation is affected by metal binding to N-MBDs (32,33).…”

“…In our laboratory, we have observed that N-MBDs of Archaeoglobus fulgidus CopA, a Cu ϩ -ATPase, and CopB, a Cu 2ϩ -ATPase with a His-rich N-MBD, control the turnover rate of these enzymes but do not affect metal binding to the transport site (32,33). Specifically, the rate-limiting conformational change associated with metal release/dephosphorylation is affected by metal binding to N-MBDs (32,33). Thus, N-MBDs, although not essential for activity, are key regula-* This work was supported by National Science Foundation Grant MCM-0235165 (to J. M.…”