PDBsum entry 2kmx

Hydrolase

PDB id: 2kmx

Contents

Protein chain

185 a.a. *

Ligands

ATP

* Residue conservation analysis

PDB id:

2kmx

Name:

Hydrolase

Title:

Solution structure of the nucleotide binding domain of the human menkes protein in the atp-bound form

Structure:

Copper-transporting atpase 1. Chain: a. Fragment: nucleotide binding domain. Synonym: copper pump 1, menkes disease-associated protein. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

L.Banci,I.Bertini,F.Cantini,S.Inagaki,M.Migliardi,A.Rosato

Key ref:

L.Banci et al. (2010). The binding mode of ATP revealed by the solution structure of the N-domain of human ATP7A. J Biol Chem, 285, 2537-2544. PubMed id: 19917612 DOI: 10.1074/jbc.M109.054262

Date:

05-Aug-09 Release date: 01-Dec-09

Protein chain

Q04656  (ATP7A_HUMAN) -  Copper-transporting ATPase 1 from Homo sapiens

Seq: 1500 a.a.

Struc: 185 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.7.2.2.8 - P-type Cu(+) transporter.
• Reaction: Cu⁺(in) + ATP + H2O = Cu⁺(out) + ADP + phosphate + H⁺

Cu(+)(in) (Bound ligand (Het Group name = ATP) corresponds exactly) + ATP + H2O = Cu(+)(out) + ADP + phosphate + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M109.054262

J Biol Chem 285:2537-2544 (2010)

PubMed id: 19917612

The binding mode of ATP revealed by the solution structure of the N-domain of human ATP7A.

L.Banci, I.Bertini, F.Cantini, S.Inagaki, M.Migliardi, A.Rosato.

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.

Selected figure(s)

Figure 1.
Solution structures of ATP-bound N-MNK (A) and ATP-free N-MNK (B). The average backbone RMSD between ATP-free and ATP-bound N-MNK domains is of 1.01 Å. The secondary structure elements comprise residues 1054–1061 (β1), 1070–1081 (α1), 1090–1100 (α2), 1108–1114 (β2), 1118–1124 (β3), 1178–1183 (β4), 1186–1190 (α3), 1197–1209 (α4), 1212–1218 (β5), and 1221–1230 (β6) for ATP-bound N-MNK and residues 1054–1061 (β1), 1070–1080 (α1), 1087–1100 (α2), 1110–1114 (β2), 1118–1123 (β3), 1178–1183 (β4), 1186–1191 (α3), 1197–1209 (α4), 1212–1218 (β5), and 1221–1230 (β6) for ATP-free N-MNK, respectively. Top panels, the radius of the tubes is proportional to the backbone RMSD of each residue. The unstructured loop was omitted for simplicity. Bottom panel, the backbone traces for the twenty lowest energy conformers are superimposed. The unstructured loop is shown in blue.

Figure 5.
ATP-binding mode of N-MNK. A, the structure of ATP-bound N-MNK showing the side chains of hydrophobic amino acids in blue and of Glu^1081 in yellow, which are in contact with the ATP molecule. The unstructured loop was omitted for simplicity. In the zoom on the ATP-binding cavity, the amino acids are labeled. B, overlay of the structures of ATP-free (pink) and ATP-bound (red) N-MNK, highlighting the regions of structural variation.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2010, 285, 2537-2544) copyright 2010.

Figures were selected by the author.