View source for 2lqb


==Metal binding repeat 2 of the Wilson disease protein (ATP7B)==
<StructureSection load='2lqb' size='340' side='right'caption='[[2lqb]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2lqb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LQB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lqb OCA], [https://pdbe.org/2lqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lqb RCSB], [https://www.ebi.ac.uk/pdbsum/2lqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lqb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ATP7B_HUMAN ATP7B_HUMAN] Defects in ATP7B are the cause of Wilson disease (WD) [MIM:[https://omim.org/entry/277900 277900]. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.<ref>PMID:8298641</ref> <ref>PMID:7626145</ref> <ref>PMID:8533760</ref> <ref>PMID:8938442</ref> <ref>PMID:8931691</ref> <ref>PMID:8782057</ref> <ref>PMID:9311736</ref> <ref>PMID:9772425</ref> <ref>PMID:9222767</ref> <ref>PMID:8980283</ref> <ref>PMID:9887381</ref> <ref>PMID:9482578</ref> <ref>PMID:9554743</ref> <ref>PMID:9452121</ref> <ref>PMID:9671269</ref> <ref>PMID:9829905</ref> <ref>PMID:10194254</ref> <ref>PMID:10447265</ref> <ref>PMID:10502776</ref> <ref>PMID:10502777</ref> <ref>PMID:10051024</ref> <ref>PMID:10544227</ref> <ref>PMID:10453196</ref> <ref>PMID:11216666</ref> <ref>PMID:11093740</ref> <ref>PMID:10790207</ref> <ref>PMID:10721669</ref> <ref>PMID:11043508</ref> <ref>PMID:11180609</ref> <ref>PMID:11690702</ref> <ref>PMID:11243728</ref> <ref>PMID:11954751</ref> <ref>PMID:12544487</ref> <ref>PMID:12325021</ref> <ref>PMID:12376745</ref> <ref>PMID:14986826</ref> <ref>PMID:14639035</ref> <ref>PMID:15024742</ref> <ref>PMID:15557537</ref> <ref>PMID:14966923</ref> <ref>PMID:15845031</ref> <ref>PMID:15811015</ref> <ref>PMID:15952988</ref> <ref>PMID:16207219</ref> <ref>PMID:16283883</ref> <ref>PMID:16088907</ref> <ref>PMID:15967699</ref> <ref>PMID:17718866</ref> <ref>PMID:18373411</ref> <ref>PMID:18203200</ref> <ref>PMID:21682854</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ATP7B_HUMAN ATP7B_HUMAN] Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human copper transporters ATP7B and ATP7A have been implicated in tumor resistance to cisplatin, a widely used anticancer drug. Cisplatin binds to the copper-binding sites in the N-terminal domain of ATP7B, and this binding may be an essential step of cisplatin detoxification involving copper ATPases. Here we demonstrate that cisplatin and a related platinum drug carboplatin produce the same adduct upon reaction with metal-binding repeat 2 (MBD2), where platinum is bound to the side chains of cysteine residues in the CxxC copper-binding motif. This suggests the same mechanism for detoxification of both drugs by ATP7B. Platinum can be also transferred to MBD2 from copper chaperone Atox1, which was previously shown to bind cisplatin. Binding of the free cisplatin and reaction with cisplatin-loaded Atox1 produce the same protein bound platinum intermediate. Transfer of platinum along the copper-transport pathways in the cell may serve as a mechanism of drug delivery to its target in the cell nucleus, and explain tumor cell resistance to cisplatin associated with overexpression of copper transporters ATP7B and ATP7A.

Copper chaperone Atox1 interacts with the metal-binding domain of Wilson disease protein in cisplatin detoxification.,Dolgova NV, Nokhrin S, Yu CH, George GN, Dmitriev OY Biochem J. 2013 Jun 11. PMID:23751120<ref>PMID:23751120</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2lqb" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dmitriev OY]]
[[Category: Dolgova NV]]
[[Category: Nokhrin S]]
[[Category: Yu C]]