1kvj
Solution Structure of the Cu(I) bound form of the first heavy metal binding motif of the Menkes protein
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OverviewOverview
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.
DiseaseDisease
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 StructureAbout this Structure
1KVJ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Copper-exporting ATPase, with EC number 3.6.3.4 Full crystallographic information is available from OCA.
ReferenceReference
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
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