ABSTRACT
Menkes’ disease, first characterized by Menkes et al. in 1962 [15], is caused by a disorder in copper metabolism [16,17]. Specifically it involves an X-chromosome linked recessive disorder in cellular copper export and normally results in death in early childhood. There occurs a severe and long-term deficiency of copper that results in progressive neurological deterioration, probably due to the impairment of crosslinking of elastin and collagen by the copper protein lysyl oxidase. The gene respon sible for Menkes’ disease encodes a CPx-type ATPase [18] that is localized in the trans-Golgi network of cells and is thought to move copper across intracellular mem branes into the secretory pathway [19]. The complete ATPase is a complex multidomain, transmembrane protein, but close to the N terminus and within the cytosol there are six metal binding domains, mbdl-6, each containing a GMTCxxC sequence motif [20-22]. It has been established [23] that each of the N-terminal domains binds one Cu(I) ion selectively relative to other metals such as Cd, Co and Zn, and since patients suffering from Menkes’ disease are deficient in copper these N-terminal domains may somehow be specific for binding copper.