1yju
From Proteopedia
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'''Solution structure of the apo form of the sixth soluble domain of Menkes protein'''<br /> | '''Solution structure of the apo form of the sixth soluble domain of Menkes protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Menkes disease is a fatal disease that can be induced by various mutations | + | Menkes disease is a fatal disease that can be induced by various mutations in the ATP7A gene, leading to unpaired uptake of dietary copper. The ATP7A gene encodes a copper(I)-translocating ATPase. Here the disease-causing A629P mutation, which occurs in the last of the six copper(I)-binding soluble domains of the ATPase (hereafter MNK6), was investigated. To understand why this apparently minor amino acid replacement is pathogenic, the solution structures and dynamics on various time-scales of wild-type and A629P-MNK6 were determined both in the apo- and copper(I)-loaded forms. The interaction in vitro with the physiological ATP7A copper(I)-donor (HAH1) was additionally studied. The A629P mutation makes the protein beta-sheet more solvent accessible, possibly resulting in an enhanced susceptibility of ATP7A to proteolytic cleavage and/or in reduced capability of copper(I)-translocation. A small reduction of the affinity for copper(I) is also observed. Both effects could concur to pathogenicity. |
==Disease== | ==Disease== | ||
| - | Known diseases associated with this structure: Analgesia from kappa-opioid receptor agonist, female-specific OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555 155555]], | + | Known diseases associated with this structure: Analgesia from kappa-opioid receptor agonist, female-specific , OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555 155555]], Cutis laxa, neonatal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300011 300011]], Melanoma susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555 155555]], Menkes disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300011 300011]], Occipital horn syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300011 300011]], Oculocutaneous albinism, type II, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555 155555]], Skin/hair/eye pigmentation 2, blond hair/fair skin OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555 155555]], Skin/hair/eye pigmentation 2, red hair/fair skin OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555 155555]], UV-induced skin damage OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555 155555]] |
==About this Structure== | ==About this Structure== | ||
| - | 1YJU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http:// | + | 1YJU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YJU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Migliardi, M.]] | [[Category: Migliardi, M.]] | ||
[[Category: Rosato, A.]] | [[Category: Rosato, A.]] | ||
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: Wang, S.]] | [[Category: Wang, S.]] | ||
[[Category: copper(i)]] | [[Category: copper(i)]] | ||
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[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:06:04 2008'' |
Revision as of 14:06, 21 February 2008
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Solution structure of the apo form of the sixth soluble domain of Menkes protein
Contents |
Overview
Menkes disease is a fatal disease that can be induced by various mutations in the ATP7A gene, leading to unpaired uptake of dietary copper. The ATP7A gene encodes a copper(I)-translocating ATPase. Here the disease-causing A629P mutation, which occurs in the last of the six copper(I)-binding soluble domains of the ATPase (hereafter MNK6), was investigated. To understand why this apparently minor amino acid replacement is pathogenic, the solution structures and dynamics on various time-scales of wild-type and A629P-MNK6 were determined both in the apo- and copper(I)-loaded forms. The interaction in vitro with the physiological ATP7A copper(I)-donor (HAH1) was additionally studied. The A629P mutation makes the protein beta-sheet more solvent accessible, possibly resulting in an enhanced susceptibility of ATP7A to proteolytic cleavage and/or in reduced capability of copper(I)-translocation. A small reduction of the affinity for copper(I) is also observed. Both effects could concur to pathogenicity.
Disease
Known diseases associated with this structure: Analgesia from kappa-opioid receptor agonist, female-specific , OMIM:[155555], Cutis laxa, neonatal OMIM:[300011], Melanoma susceptibility to OMIM:[155555], Menkes disease OMIM:[300011], Occipital horn syndrome OMIM:[300011], Oculocutaneous albinism, type II, modifier of OMIM:[155555], Skin/hair/eye pigmentation 2, blond hair/fair skin OMIM:[155555], Skin/hair/eye pigmentation 2, red hair/fair skin OMIM:[155555], UV-induced skin damage OMIM:[155555]
About this Structure
1YJU is a Single protein structure of sequence from Homo sapiens. Active as Copper-exporting ATPase, with EC number 3.6.3.4 Full crystallographic information is available from OCA.
Reference
An atomic-level investigation of the disease-causing A629P mutant of the Menkes protein, ATP7A., Banci L, Bertini I, Cantini F, Migliardi M, Rosato A, Wang S, J Mol Biol. 2005 Sep 16;352(2):409-17. PMID:16083905
Page seeded by OCA on Thu Feb 21 16:06:04 2008
Categories: Copper-exporting ATPase | Homo sapiens | Single protein | Banci, L. | Bertini, I. | Cantini, F. | Migliardi, M. | Rosato, A. | SPINE, Structural Proteomics in Europe. | Wang, S. | Copper(i) | Metal homeostasis | Metallochaperone | Protein-protein interaction | Spine | Structural genomics | Structural proteomics in europe
