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{{STRUCTURE_2arf| PDB=2arf | SCENE= }} | |||
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'''Solution structure of the Wilson ATPase N-domain in the presence of ATP''' | '''Solution structure of the Wilson ATPase N-domain in the presence of ATP''' | ||
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[[Category: Morgan, C T.]] | [[Category: Morgan, C T.]] | ||
[[Category: Tsivkovskii, R.]] | [[Category: Tsivkovskii, R.]] | ||
[[Category: | [[Category: Atp binding]] | ||
[[Category: | [[Category: Atpase]] | ||
[[Category: | [[Category: Copper transport]] | ||
[[Category: | [[Category: Nucleotide binding]] | ||
[[Category: | [[Category: P-type atpase,atp7b]] | ||
[[Category: | [[Category: Wilson disease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:23:02 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 19:23, 3 May 2008
Solution structure of the Wilson ATPase N-domain in the presence of ATP
OverviewOverview
Wilson disease protein (ATP7B) is a copper-transporting P(1B)-type ATPase that regulates copper homeostasis and biosynthesis of copper-containing enzymes in human tissues. Inactivation of ATP7B or related ATP7A leads to severe neurodegenerative disorders, whereas their overexpression contributes to cancer cell resistance to chemotherapeutics. Copper-transporting ATPases differ from other P-type ATPases in their topology and the sequence of their nucleotide-binding domain (N-domain). To gain insight into the structural basis of ATP7B function, we have solved the structure of the ATP7B N-domain in the presence of ATP by using heteronuclear multidimensional NMR spectroscopy. The N-domain consists of a six-stranded beta-sheet with two adjacent alpha-helical hairpins and, unexpectedly, shows higher similarity to the bacterial K(+)-transporting ATPase KdpB than to the mammalian Ca(2+)-ATPase or Na(+),K(+)-ATPase. The common core structure of P-type ATPases is retained in the 3D fold of the N-domain; however, the nucleotide coordination environment of ATP7B within this fold is different. The residues H1069, G1099, G1101, I1102, G1149, and N1150 conserved in the P(1B)-ATPase subfamily contribute to ATP binding. Analysis of the frequent disease mutation H1069Q demonstrates that this mutation does not significantly affect the structure of the N-domain but prevents tight binding of ATP. The structure of the N-domain accounts for the disruptive effects of >30 known Wilson disease mutations. The unique features of the N-domain provide a structural basis for the development of specific inhibitors and regulators of ATP7B.
DiseaseDisease
Known disease associated with this structure: Wilson disease OMIM:[606882]
About this StructureAbout this Structure
2ARF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the N-domain of Wilson disease protein: distinct nucleotide-binding environment and effects of disease mutations., Dmitriev O, Tsivkovskii R, Abildgaard F, Morgan CT, Markley JL, Lutsenko S, Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5302-7. Epub 2006 Mar 27. PMID:16567646 Page seeded by OCA on Sat May 3 19:23:02 2008