2arf
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= | |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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= ATP7B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ATP7B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2arf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2arf OCA], [http://www.ebi.ac.uk/pdbsum/2arf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2arf RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Wilson disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606882 606882]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Tsivkovskii, R.]] | [[Category: Tsivkovskii, R.]] | ||
[[Category: atp binding]] | [[Category: atp binding]] | ||
| - | [[Category: atp7b]] | ||
[[Category: atpase]] | [[Category: atpase]] | ||
[[Category: copper transport]] | [[Category: copper transport]] | ||
[[Category: nucleotide binding]] | [[Category: nucleotide binding]] | ||
| - | [[Category: p-type atpase]] | + | [[Category: p-type atpase,atp7b]] |
[[Category: wilson disease]] | [[Category: wilson disease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:56:16 2008'' |
Revision as of 22:56, 30 March 2008
| |||||||
| Gene: | ATP7B (Homo sapiens) | ||||||
| Activity: | Copper-exporting ATPase, with EC number 3.6.3.4 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Solution structure of the Wilson ATPase N-domain in the presence of ATP
Contents |
Overview
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.
Disease
Known disease associated with this structure: Wilson disease OMIM:[606882]
About this Structure
2ARF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:16567646
Page seeded by OCA on Mon Mar 31 01:56:16 2008
