1KVI

Solution Structure of the Reduced Form of the First Heavy Metal Binding Motif of the Menkes Protein

1KVI の概要

• エントリーDOI: 10.2210/pdb1kvi/pdb
• 関連するPDBエントリー: 1KVJ
• 分子名称: Copper-transporting ATPase 1 (1 entity in total)
• 機能のキーワード: menkes, cu-protein, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein. Isoform 3: Cytoplasm, cytosol (Probable). Isoform 5: Endoplasmic reticulum: Q04656
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8691.85

構造登録者

De Silva, T.M.,Veglia, G.,Opella, S.J. (登録日: 2002-01-26, 公開日: 2003-11-18, 最終更新日: 2024-05-22)

主引用文献

DeSilva, T.M.,Veglia, G.,Opella, S.J.
Solution structures of the reduced and Cu(I) bound forms of the first metal binding sequence of ATP7A associated with Menkes disease.
Proteins, 61:1038-1049, 2005

PubMed Abstract: 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.

PubMed: 16211579
DOI: 10.1002/prot.20639

実験手法

SOLUTION NMR