2KMX: Solution structure of the nucleotide binding domain of the human Menkes protein in the ATP-bound form

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.
PDB ID: 2KMXDownload
MMDB ID: 78386
PDB Deposition Date: 2009/8/5
Updated in MMDB: 2009/12
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Molecular Components in 2KMX
Label Count Molecule
Protein (1 molecule)
Copper-transporting Atpase 1(Gene symbol: ATP7A)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB