1kvj - Revision history

OCA at 08:43, 22 May 2024

OCA — Wed, 22 May 2024 08:43:09 GMT

←Older revision		Revision as of 08:43, 22 May 2024
Line 22:		Line 22:
	</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=1kvj ConSurf].		</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=1kvj ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The coding sequence for the first N-terminal copper binding motif of the human Menkes disease protein (MNK1; residues 2-79) was synthesized, cloned, and expressed in bacteria for biochemical and structural studies. MNK1 adopts the betaalphabetabetaalphabeta fold common to all the metal binding sequences (MBS) found in other metal transport systems (e.g., the yeast copper chaperone for superoxide dismutase CCS, the yeast copper chaperone ATX1 bound to Hg(II), and most recently Cu(I), the bacterial copper binding protein, CopZ, and the bacterial Hg(II) binding protein MerP), although substantial differences were found in the metal binding loop. Similar to ATX1, MNK1 binds Cu(I) in a distorted linear bicoordinate geometry. As with MerP, MNK1 has a high affinity for both Hg(II) and Cu(I), although it displays a marked preference for Cu(I). In addition, we found that F71 is a key residue in the compact folding of MNK1, and its mutation to alanine results in an unfolded structure. The homologous residue in MerP has also been mutated with similar results. Finally, to understand the relationship between protein folding and metal affinity and specificity, we expressed a chimeric MBS with the MNK1 protein carrying the binding motif of MerP (CAAC-MNK1); this chimeric protein showed differences in structure and the dynamics of the binding site that may account for metal specificity.
		+
		+	Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease.,DeSilva TM, Veglia G, Opella SJ Proteins. 2005 Dec 1;61(4):1038-49. PMID:16211579<ref>PMID:16211579</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 08:04, 3 April 2024

OCA — Wed, 03 Apr 2024 08:04:10 GMT

←Older revision		Revision as of 08:04, 3 April 2024
Line 1:		Line 1:

	==Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein==		==Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein==
-	<StructureSection load='1kvj' size='340' side='right'caption='[[1kvj~~]], [[NMR_Ensembles_of_Models \| 10 NMR models~~]]' scene=''>	+	<StructureSection load='1kvj' size='340' side='right'caption='[[1kvj]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1kvj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1kvj]] 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>
-	</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>	+	</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='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[1kvi\|1kvi]]</div></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~~='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/Copper-exporting_ATPase Copper-exporting ATPase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [https://pdbe.org/1kvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [https://www.ebi.ac.uk/pdbsum/1kvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kvj ProSAT]</span></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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [https://pdbe.org/1kvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [https://www.ebi.ac.uk/pdbsum/1kvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kvj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[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 ==		== 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.	+	[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 ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 23:		Line 22:
	</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=1kvj ConSurf].		</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=1kvj ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The coding sequence for the first N-terminal copper binding motif of the human Menkes disease protein (MNK1; residues 2-79) was synthesized, cloned, and expressed in bacteria for biochemical and structural studies. MNK1 adopts the betaalphabetabetaalphabeta fold common to all the metal binding sequences (MBS) found in other metal transport systems (e.g., the yeast copper chaperone for superoxide dismutase CCS, the yeast copper chaperone ATX1 bound to Hg(II), and most recently Cu(I), the bacterial copper binding protein, CopZ, and the bacterial Hg(II) binding protein MerP), although substantial differences were found in the metal binding loop. Similar to ATX1, MNK1 binds Cu(I) in a distorted linear bicoordinate geometry. As with MerP, MNK1 has a high affinity for both Hg(II) and Cu(I), although it displays a marked preference for Cu(I). In addition, we found that F71 is a key residue in the compact folding of MNK1, and its mutation to alanine results in an unfolded structure. The homologous residue in MerP has also been mutated with similar results. Finally, to understand the relationship between protein folding and metal affinity and specificity, we expressed a chimeric MBS with the MNK1 protein carrying the binding motif of MerP (CAAC-MNK1); this chimeric protein showed differences in structure and the dynamics of the binding site that may account for metal specificity.
-
-	Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease.,DeSilva TM, Veglia G, Opella SJ Proteins. 2005 Dec 1;61(4):1038-49. PMID:16211579<ref>PMID:16211579</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 39:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Copper-exporting ATPase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Opella, S J~~]]	+	[[Category: De Silva TM]]
-	[[Category: ~~Silva, T M.De~~]]	+	[[Category: Opella SJ]]
-	[[Category: Veglia, G]]	+	[[Category: Veglia G]]
-	~~[[Category: Cu-bound]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Menke~~]]	+

OCA at 08:11, 23 February 2022

OCA — Wed, 23 Feb 2022 08:11:15 GMT

←Older revision		Revision as of 08:11, 23 February 2022
Line 32:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[ATPase 3D structures\|ATPase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:50, 21 April 2021

OCA — Wed, 21 Apr 2021 08:50:58 GMT

←Older revision		Revision as of 08:50, 21 April 2021
Line 3:		Line 3:
	<StructureSection load='1kvj' size='340' side='right'caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='1kvj' size='340' side='right'caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1kvj]] 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1kvj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene></td></tr>	+	</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kvi\|1kvi]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Copper-exporting_ATPase Copper-exporting ATPase], with EC number [https://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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [~~http~~://pdbe.org/1kvj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1kvj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1kvj ProSAT]</span></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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [https://pdbe.org/1kvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [https://www.ebi.ac.uk/pdbsum/1kvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kvj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[[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 ==		== 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.	+	[[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 ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[ATPase 3D structures\|ATPase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:41, 17 July 2019

OCA — Wed, 17 Jul 2019 13:41:45 GMT

←Older revision		Revision as of 13:41, 17 July 2019
Line 1:		Line 1:

	==Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein==		==Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein==
-	<StructureSection load='1kvj' size='340' side='right' caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>	+	<StructureSection load='1kvj' size='340' side='right'caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1kvj]] 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1kvj]] 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>
Line 17:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/1kvj_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/1kvj_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 32:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[ATPase 3D structures\|ATPase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 41:
	[[Category: Copper-exporting ATPase]]		[[Category: Copper-exporting ATPase]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Opella, S J]]		[[Category: Opella, S J]]
	[[Category: Silva, T M.De]]		[[Category: Silva, T M.De]]

OCA at 07:30, 11 October 2017

OCA — Wed, 11 Oct 2017 07:30:24 GMT

←Older revision		Revision as of 07:30, 11 October 2017
Line 1:		Line 1:
		+
	==Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein==		==Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein==
	<StructureSection load='1kvj' size='340' side='right' caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='1kvj' size='340' side='right' caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</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='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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [http://pdbe.org/1kvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [http://www.ebi.ac.uk/pdbsum/1kvj PDBsum]</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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [http://pdbe.org/1kvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [http://www.ebi.ac.uk/pdbsum/1kvj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1kvj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</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=1kvj ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 31:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[ATPase\|ATPase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 00:17, 12 September 2015

OCA — Sat, 12 Sep 2015 00:17:04 GMT

←Older revision		Revision as of 00:17, 12 September 2015
Line 2:		Line 2:
	<StructureSection load='1kvj' size='340' side='right' caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='1kvj' size='340' side='right' caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1kvj]] is a 1 chain structure with 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1kvj]] 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</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='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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [http://www.ebi.ac.uk/pdbsum/1kvj PDBsum]</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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [http://pdbe.org/1kvj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [http://www.ebi.ac.uk/pdbsum/1kvj PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 30:		Line 30:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1kvj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Copper-exporting ATPase]]		[[Category: Copper-exporting ATPase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Opella, S J]]		[[Category: Opella, S J]]
	[[Category: Silva, T M.De]]		[[Category: Silva, T M.De]]

OCA at 16:12, 5 January 2015

OCA — Mon, 05 Jan 2015 16:12:54 GMT

←Older revision		Revision as of 16:12, 5 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1kvj]] is a 1 chain structure with 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1kvj]] is a 1 chain structure with 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</td></tr>
-	<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [http://www.ebi.ac.uk/pdbsum/1kvj PDBsum]</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=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [http://www.ebi.ac.uk/pdbsum/1kvj PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== 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>		[[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>
Line 39:		Line 39:
	[[Category: Copper-exporting ATPase]]		[[Category: Copper-exporting ATPase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Opella, S J.]]	+	[[Category: Opella, S J]]
-	[[Category: Silva, T M.De.]]	+	[[Category: Silva, T M.De]]
-	[[Category: Veglia, G.]]	+	[[Category: Veglia, G]]
	[[Category: Cu-bound]]		[[Category: Cu-bound]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Menke]]		[[Category: Menke]]

OCA at 16:14, 29 September 2014

OCA — Mon, 29 Sep 2014 16:14:00 GMT

←Older revision		Revision as of 16:14, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1kvj\| PDB=1kvj \| SCENE= }}~~	+	==Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein==
-	===Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein===	+	<StructureSection load='1kvj' size='340' side='right' caption='[[1kvj]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_16211579}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1kvj]] is a 1 chain structure with 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=1KVJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KVJ FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1kvi\|1kvi]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1kvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kvj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kvj RCSB], [http://www.ebi.ac.uk/pdbsum/1kvj 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/kv/1kvj_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/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The coding sequence for the first N-terminal copper binding motif of the human Menkes disease protein (MNK1; residues 2-79) was synthesized, cloned, and expressed in bacteria for biochemical and structural studies. MNK1 adopts the betaalphabetabetaalphabeta fold common to all the metal binding sequences (MBS) found in other metal transport systems (e.g., the yeast copper chaperone for superoxide dismutase CCS, the yeast copper chaperone ATX1 bound to Hg(II), and most recently Cu(I), the bacterial copper binding protein, CopZ, and the bacterial Hg(II) binding protein MerP), although substantial differences were found in the metal binding loop. Similar to ATX1, MNK1 binds Cu(I) in a distorted linear bicoordinate geometry. As with MerP, MNK1 has a high affinity for both Hg(II) and Cu(I), although it displays a marked preference for Cu(I). In addition, we found that F71 is a key residue in the compact folding of MNK1, and its mutation to alanine results in an unfolded structure. The homologous residue in MerP has also been mutated with similar results. Finally, to understand the relationship between protein folding and metal affinity and specificity, we expressed a chimeric MBS with the MNK1 protein carrying the binding motif of MerP (CAAC-MNK1); this chimeric protein showed differences in structure and the dynamics of the binding site that may account for metal specificity.

-	~~==Disease==~~	+	Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease.,DeSilva TM, Veglia G, Opella SJ Proteins. 2005 Dec 1;61(4):1038-49. PMID:16211579<ref>PMID:16211579</ref>
-	~~[[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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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~~.	+	</div>
-		+
-	~~==About this Structure==~~	+
-	~~[[1kvj]] is a 1 chain structure with 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=1KVJ OCA].~~	+

	==See Also==		==See Also==
	*[[ATPase\|ATPase]]		*[[ATPase\|ATPase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:016211579</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Copper-exporting ATPase]]		[[Category: Copper-exporting ATPase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 04:05, 25 March 2013

OCA — Mon, 25 Mar 2013 04:05:38 GMT

←Older revision		Revision as of 04:05, 25 March 2013
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-	[[Image:1kvj.png\|left\|200px]]
-
	{{STRUCTURE_1kvj\| PDB=1kvj \| SCENE= }}		{{STRUCTURE_1kvj\| PDB=1kvj \| SCENE= }}
-
	===Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein===		===Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein===
		+	{{ABSTRACT_PUBMED_16211579}}

-	~~{{ABSTRACT_PUBMED_16211579}}~~	+	==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.

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:016211579</ref><references group="xtra"/>	+	<ref group="xtra">PMID:016211579</ref><references group="xtra"/><references/>
	[[Category: Copper-exporting ATPase]]		[[Category: Copper-exporting ATPase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]