2KMV

Solution structure of the nucleotide binding domain of the human Menkes protein in the ATP-free form

Summary for 2KMV

• Entry DOI: 10.2210/pdb2kmv/pdb
• Related: 2kmx
• NMR Information: BMRB: 16440
• Descriptor: Copper-transporting ATPase 1 (1 entity in total)
• Functional Keywords: atp7a, menkes, atpase, nucleotide binding protein, 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
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 20269.80

Authors

Banci, L.,Bertini, I.,Cantini, F.,Inagaki, S.,Migliardi, M.,Rosato, A. (deposition date: 2009-08-05, release date: 2009-12-01, Last modification date: 2024-05-15)

Primary citation

Banci, L.,Bertini, I.,Cantini, F.,Inagaki, S.,Migliardi, M.,Rosato, A.
The binding mode of ATP revealed by the solution structure of the N-domain of human ATP7A.
J.Biol.Chem., 2009

PubMed Abstract: We report the solution NMR structures of the N-domain of the Menkes protein (ATP7A) in the ATP-free and ATP-bound forms. The structures consist of a twisted antiparallel six-stranded beta-sheet flanked by two pairs of alpha-helices. A protein loop of 50 amino acids located between beta 3 and beta 4 is disordered and mobile on the subnanosecond time scale. ATP binds with an affinity constant of (1.2 +/- 0.1) x 10(4) m(-1) and exchanges with a rate of the order of 1 x 10(3) s(-1). The ATP-binding cavity is considerably affected by the presence of the ligand, resulting in a more compact conformation in the ATP-bound than in the ATP-free form. This structural variation is due to the movement of the alpha1-alpha2 and beta2-beta 3 loops, both of which are highly conserved in copper(I)-transporting P(IB)-type ATPases. The present structure reveals a characteristic binding mode of ATP within the protein scaffold of the copper(I)-transporting P(IB)-type ATPases with respect to the other P-type ATPases. In particular, the binding cavity contains mainly hydrophobic aliphatic residues, which are involved in van der Waal's interactions with the adenine ring of ATP, and a Glu side chain, which forms a crucial hydrogen bond to the amino group of ATP.

PubMed: 19917612
DOI: 10.1074/jbc.M109.054262

Experimental method

SOLUTION NMR