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 β-sheet flanked by two pairs of α-helices. A protein loop of 50 amino acids located between β3 and β4 is disordered and mobile on the subnanosecond time scale.ATPbinds with an affinity constant of (1.2 ± 0.1) x 104 M-1 and exchanges with a rate of the order of 1 x 103 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 α1-α2 and β2-β3 loops, both of which are highly conserved in copper(I)-transporting PIB-type ATPases. The present structure reveals a characteristic binding mode of ATP within the protein scaffold of the copper(I)-transporting PIB-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. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

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. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 285:(2010), pp. 2537-2544. [10.1074/jbc.M109.054262]

The Binding Mode of ATP Revealed by the Solution Structure of the N-domain of Human ATP7A

BANCI, LUCIA;BERTINI, IVANO;CANTINI, FRANCESCA;MIGLIARDI, MANUELE;ROSATO, ANTONIO
2010

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 β-sheet flanked by two pairs of α-helices. A protein loop of 50 amino acids located between β3 and β4 is disordered and mobile on the subnanosecond time scale.ATPbinds with an affinity constant of (1.2 ± 0.1) x 104 M-1 and exchanges with a rate of the order of 1 x 103 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 α1-α2 and β2-β3 loops, both of which are highly conserved in copper(I)-transporting PIB-type ATPases. The present structure reveals a characteristic binding mode of ATP within the protein scaffold of the copper(I)-transporting PIB-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. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
2010
285
2537
2544
L.Banci; I.Bertini; F.Cantini; S.Inagaki; M.Migliardi; A.Rosato
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/385712
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