The clinical efficacy of the widely used anticancer drug cisplatin is severely limited by the emergence of resistance. This is related to the drug binding to proteins such as the copper influx transporter Ctr1, the copper chaperone Atox1, and the copper pumps ATP7A and ATP7B. While the binding modes of cisplatin to the first two proteins are known, the structural determinants of platinated ATP7...

Wilson disease (WD) is a severe hepato-neurologic disorder that affects primarily children and young adults. WD is caused by mutations in ATP7B and subsequent copper overload. However, copper levels alone do not predict severity of the disease. We demonstrate that temporal and spatial distribution of copper in hepatocytes may play an important role in WD pathology. High resolution synchrotron-b...

Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper inf...

Single nucleotide polymorphisms modulate the risk of developing ovarian cancer during lifetime. In this study we analyzed 12 polymorphic variants and 2 deletions in PGR, ABCB1, ABCG2, GSTT1, GSTM1, GSTP1, ATM, TP53 and ATP7B genes. Ten genetic modifications were significantly associated with the risk of developing ovarian carcinoma in at least one of the groups under study. PGR gene polymorphis...

Wilson’s disease is a rare, autosomal recessive, genetic, copper overload disease, which evokes multiple motor or neuropsychiatric symptoms and liver disease. It is the consequence of a variety of different mutations affecting the ATP7B gene. This gene encodes for a class IB, P-type, copper-transporting ATPase, which is located in the trans-Golgi network of the liver and brain, and mediates the...

Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic i...

Wilson là bệnh rối loạn chuyển hóa đồng, di truyền gen lặn trên nhiễm sắc thể thường, do đột biến ATP7B cánh dài số 13 (13q14.3) gây ra. một hiếm, tần suất gặp 1/ 30000 đến 1/50000 trẻ. Với tỷ lệ này ước tính ở Việt Nam có khoảng hơn 2000 nhân mắc này. Tuy nhiên con đã được chẩn đoán ít rất nhiều lần so với bệnh, chúng tôi mô tả trường hợp các biểu hiện tâm thần kinh không điển hình, triệu chứn...

The human copper exporters ATP7A and ATP7B contain domains common to all P-type ATPases as well as class-specific features such as six sequential heavy-metal binding domains (HMBD1-HMBD6) and a type-specific constellation of transmembrane helices. Despite the medical significance of ATP7A and ATP7B related to Menkes and Wilson diseases, respectively, structural information has only been availab...