2KIJ

Solution structure of the Actuator domain of the copper-transporting ATPase ATP7A

2KIJ の概要

• エントリーDOI: 10.2210/pdb2kij/pdb
• NMR情報: BMRB: 16277
• 分子名称: Copper-transporting ATPase 1 (1 entity in total)
• 機能のキーワード: actuator, atp7a, menkes disease, alternative splicing, atp-binding, cell membrane, copper, copper transport, cytoplasm, disease mutation, endoplasmic reticulum, glycoprotein, golgi apparatus, hydrolase, ion transport, magnesium, membrane, metal-binding, nucleotide-binding, phosphoprotein, polymorphism, transmembrane, transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12967.74

構造登録者

Banci, L.,Bertini, I.,Cantini, F.,Migliardi, M.,Nushi, F.,Natile, G.,Rosato, A. (登録日: 2009-05-06, 公開日: 2009-08-25, 最終更新日: 2024-05-15)

主引用文献

Banci, L.,Bertini, I.,Cantini, F.,Migliardi, M.,Natile, G.,Nushi, F.,Rosato, A.
Solution structures of the actuator domain of ATP7A and ATP7B, the Menkes and Wilson disease proteins
Biochemistry, 48:7849-7855, 2009

PubMed Abstract: ATP7A and ATP7B are two human P(1B)-type ATPases that have a crucial role in maintaining copper(I) homeostasis. Among the various domains of these enzymes, one, called the Actuator or A-domain, has a regulatory function and is required for the phosphatase step of the catalytic cycle (dephosphorylation of the intermediate formed during ATP hydrolysis). Here we report the solution structures of the A-domain of both proteins, solved by heteronuclear NMR spectroscopy and a characterization of the dynamics of the A-domain of ATP7A. We observed that the catalytically important TGE loop protrudes from the structure ready for interaction with the phosphorylated site in the ATP-binding domain. The loop is rigid, suggesting that the catalytic step does not require substantial structural flexibility or rearrangements. The present structures were useful to rationalize the molecular effects of disease-causing mutations. In particular, it can be concluded that mutations occurring in the A-domain either destabilize the fold of the domain (such as Gly860Val in ATP7A) or affect the network of communication within the domain (such as Leu873Arg in ATP7A) or with the other domains of the enzyme (such as Gly853Arg in ATP7A).

PubMed: 19645496
DOI: 10.1021/bi901003k

実験手法

SOLUTION NMR