2arf: Difference between revisions
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[[Image:2arf.gif|left|200px]] | [[Image:2arf.gif|left|200px]] | ||
'''Solution structure of the Wilson ATPase N-domain in the presence of ATP''' | {{Structure | ||
|PDB= 2arf |SIZE=350|CAPTION= <scene name='initialview01'>2arf</scene> | |||
|SITE= | |||
|LIGAND= | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Copper-exporting_ATPase Copper-exporting ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.4 3.6.3.4] | |||
|GENE= ATP7B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Solution structure of the Wilson ATPase N-domain in the presence of ATP''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2ARF is a [ | 2ARF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ARF OCA]. | ||
==Reference== | ==Reference== | ||
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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16567646 16567646] | ||
[[Category: Copper-exporting ATPase]] | [[Category: Copper-exporting ATPase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: wilson disease]] | [[Category: wilson disease]] | ||
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Revision as of 16:52, 20 March 2008
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| Gene: | ATP7B (Homo sapiens) | ||||||
| Activity: | Copper-exporting ATPase, with EC number 3.6.3.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 diseases 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
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