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.