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Cu 2+ ‐ATPases: Sequence Analyses and Implications in the Wilson Disease
Author(s) -
Liaw ShwuHuey,
Chuang LeeMing
Publication year - 1999
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.199900099
Subject(s) - missense mutation , chemistry , mutant , gene , peptide sequence , conserved sequence , atpase , sequence motif , transmembrane domain , menkes disease , genetics , sequence alignment , biochemistry , enzyme , biology , mutation , copper metabolism , organic chemistry , copper
Wilson disease is an autosomal recessive disorder of copper metabolism, and the defective gene codes for a P‐type Cu 2+ ‐ATPase. Sequence comparison revealed that the Cu 2+ ‐ATPases were very distinct from the Ca 2+ ‐, Na + ‐ H + ‐, and K + ‐ATPases, which however, shared significant similarity to each other. The major difference may be due to the difference in metal ligand preference. Some novel conserved motifs in the Wilson disease protein were also identified, including a putative Walker A motif (GCGIGCKV, residues 1099–1106), and a Walker B motif (GDGVND, residues 1266–1271) for the cofactor ATP binding and hydrolysis, a unique KAPIQ motif (residues 910–914) in the transduction domain, and some motifs in the transmembrane segments probably for the substrate specificity. Combining with the previous genetic and biochemical data, some conserved residues could be assigned for possible functions. This information should provide a guide for designing future studies of structure‐function relationships in the Wilson disease gene. Sequence analysis is also useful in distinguishing whether the mutant residues are missense or polymorphism, such as T977M was identified as a missense mutation because only small amino acid residues appear at this position.