View source for 2kij

==Solution structure of the Actuator domain of the copper-transporting ATPase ATP7A==
<StructureSection load='2kij' size='340' side='right' caption='[[2kij]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kij]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KIJ FirstGlance]. <br>
</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kij FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kij OCA], [http://pdbe.org/2kij PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kij RCSB], [http://www.ebi.ac.uk/pdbsum/2kij PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/ATP7A_HUMAN ATP7A_HUMAN]] Defects in ATP7A are the cause of Menkes disease (MNKD) [MIM:[http://omim.org/entry/309400 309400]]; also known as kinky hair disease. MNKD is an X-linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes.<ref>PMID:10079817</ref> <ref>PMID:7977350</ref> <ref>PMID:8981948</ref> <ref>PMID:10401004</ref> <ref>PMID:10319589</ref> <ref>PMID:11241493</ref> <ref>PMID:11350187</ref> <ref>PMID:15981243</ref> <ref>PMID:22992316</ref>   Defects in ATP7A are the cause of occipital horn syndrome (OHS) [MIM:[http://omim.org/entry/304150 304150]]; also known as X-linked cutis laxa. OHS is an X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities included occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga.<ref>PMID:9246006</ref> <ref>PMID:17108763</ref>   Defects in ATP7A are a cause of distal spinal muscular atrophy X-linked type 3 (DSMAX3) [MIM:[http://omim.org/entry/300489 300489]]. DSMAX3 is a neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.<ref>PMID:20170900</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/ATP7A_HUMAN ATP7A_HUMAN]] May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kij_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kij ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ATP7A and ATP7B are two human P(1B)-type ATPases that have a crucial role in maintaining copper(I) homeostasis. Among the various domains of these enzymes, one, called the Actuator or A-domain, has a regulatory function and is required for the phosphatase step of the catalytic cycle (dephosphorylation of the intermediate formed during ATP hydrolysis). Here we report the solution structures of the A-domain of both proteins, solved by heteronuclear NMR spectroscopy and a characterization of the dynamics of the A-domain of ATP7A. We observed that the catalytically important TGE loop protrudes from the structure ready for interaction with the phosphorylated site in the ATP-binding domain. The loop is rigid, suggesting that the catalytic step does not require substantial structural flexibility or rearrangements. The present structures were useful to rationalize the molecular effects of disease-causing mutations. In particular, it can be concluded that mutations occurring in the A-domain either destabilize the fold of the domain (such as Gly860Val in ATP7A) or affect the network of communication within the domain (such as Leu873Arg in ATP7A) or with the other domains of the enzyme (such as Gly853Arg in ATP7A).

Solution structures of the actuator domain of ATP7A and ATP7B, the Menkes and Wilson disease proteins.,Banci L, Bertini I, Cantini F, Migliardi M, Natile G, Nushi F, Rosato A Biochemistry. 2009 Aug 25;48(33):7849-55. PMID:19645496<ref>PMID:19645496</ref>

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

==See Also==
*[[ATPase|ATPase]]
*[[P(1B)-Type Cu(I) Transporting ATPases ATP7A and ATP7B|P(1B)-Type Cu(I) Transporting ATPases ATP7A and ATP7B]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Copper-exporting ATPase]]
[[Category: Human]]
[[Category: Banci, L]]
[[Category: Bertini, I]]
[[Category: Cantini, F]]
[[Category: Migliardi, M]]
[[Category: Natile, G]]
[[Category: Nushi, F]]
[[Category: Rosato, A]]
[[Category: Actuator]]
[[Category: Atp-binding]]
[[Category: Atp7a]]
[[Category: Cell membrane]]
[[Category: Copper transport]]
[[Category: Disease mutation]]
[[Category: Endoplasmic reticulum]]
[[Category: Glycoprotein]]
[[Category: Golgi apparatus]]
[[Category: Hydrolase]]
[[Category: Ion transport]]
[[Category: Magnesium]]
[[Category: Membrane]]
[[Category: Menkes disease]]
[[Category: Metal-binding]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Transmembrane]]
[[Category: Transport]]