2ga7: Difference between revisions
New page: left|200px<br /> <applet load="2ga7" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ga7" /> '''Solution structure of the copper(I) form of... |
No edit summary |
||
| (17 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Solution structure of the copper(I) form of the third metal-binding domain of ATP7A protein (menkes disease protein)== | ||
The third metal-binding domain of the human Menkes protein (MNK3), a | <StructureSection load='2ga7' size='340' side='right'caption='[[2ga7]]' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ga7]] 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=2GA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GA7 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene></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=2ga7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ga7 OCA], [https://pdbe.org/2ga7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ga7 RCSB], [https://www.ebi.ac.uk/pdbsum/2ga7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ga7 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/ATP7A_HUMAN ATP7A_HUMAN] Defects in ATP7A are the cause of Menkes disease (MNKD) [MIM:[https://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:[https://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:[https://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 == | |||
[https://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/ga/2ga7_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=2ga7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The third metal-binding domain of the human Menkes protein (MNK3), a copper(I)-transporting ATPase, has been expressed in Escherichia coli and characterized in solution. The solution structure of MNK3, its copper(I)-binding properties, and its interaction with the physiological partner, HAH1, have been studied. MNK3 is the domain most dissimilar in structure from the other domains of the Menkes protein. This is reflected in a significant rearrangement of the last strand of the four-stranded beta-sheet when compared with the other known homologous proteins or protein domains. MNK3 is also peculiar with respect to its interaction with the copper(I) ion, as it was found to be a comparatively weak binder. Copper(I) transfer from metal-loaded HAH1 was observed experimentally, but the metal distribution was shifted toward binding by HAH1. This is at variance with what is observed for the other Menkes domains. | |||
Solution structure and intermolecular interactions of the third metal-binding domain of ATP7A, the Menkes disease protein.,Banci L, Bertini I, Cantini F, DellaMalva N, Herrmann T, Rosato A, Wuthrich K J Biol Chem. 2006 Sep 29;281(39):29141-7. Epub 2006 Jul 26. PMID:16873374<ref>PMID:16873374</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ga7" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[ATPase 3D structures|ATPase 3D structures]] | |||
[ | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Banci | [[Category: Banci L]] | ||
[[Category: Bertini | [[Category: Bertini I]] | ||
[[Category: Cantini | [[Category: Cantini F]] | ||
[[Category: DellaMalva | [[Category: DellaMalva N]] | ||
[[Category: Herrmann | [[Category: Herrmann T]] | ||
[[Category: Rosato | [[Category: Rosato A]] | ||
[[Category: Wuthrich K]] | |||
[[Category: Wuthrich | |||
