2arf

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[[Image:2arf.gif|left|200px]]
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{{STRUCTURE_2arf| PDB=2arf | SCENE= }}
{{STRUCTURE_2arf| PDB=2arf | SCENE= }}
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'''Solution structure of the Wilson ATPase N-domain in the presence of ATP'''
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===Solution structure of the Wilson ATPase N-domain in the presence of ATP===
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==Overview==
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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 &gt;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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16567646 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16567646}}
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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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].
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2ARF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ARF OCA].
==Reference==
==Reference==
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[[Category: P-type atpase,atp7b]]
[[Category: P-type atpase,atp7b]]
[[Category: Wilson disease]]
[[Category: Wilson disease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:23:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:44:23 2008''

Revision as of 14:44, 28 July 2008

Image:2arf.png

Template:STRUCTURE 2arf

Contents

Solution structure of the Wilson ATPase N-domain in the presence of ATP

Template:ABSTRACT PUBMED 16567646

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 experimental 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 Jul 28 17:44:23 2008

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