title: Structural and functional insights of Wilson disease copper-transporting ATPase.
abstract: Wilson disease is an autosomal recessive disorder of copper metabolism. The gene for this disorder has been cloned and identified to encode a copper-transporting ATPase (ATP7B), a member of a large family of cation transporters, the P-type ATPases. In addition to the core elements common to all P-type ATPases, the Wilson copper-transporting ATPase has a large cytoplasmic N-terminus comprised six heavy metal associated (HMA) domains, each of which contains the copper-binding sequence motif GMT/HCXXC. Extensive studies addressing the functional, regulatory, and structural aspects of heavy metal transport by heavy metal transporters in general, have offered great insights into copper transport by Wilson copper-transporting ATPase. The findings from these studies have been used together with homology modeling of the Wilson disease copper-transporting ATPases based on the X-ray structure of the sarcoplasmic reticulum (SR) calcium-ATPase, to present a hypothetical model of the mechanism of copper transport by copper-transporting ATPases.
authors.affiliation: Department of Structural Biology and Biochemistry Research, The Hospital for Sick, Children, Toronto, Ontario, Canada.
authors.forename: Negah
authors.initials: N
authors.lastname: Fatemi
authors.forename: Bibudhendra
authors.initials: B
authors.lastname: Sarkar
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D000252:Calcium-Transporting ATPases / Q000737:chemistry; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015032:Zinc / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D015032:Zinc