PDBsum entry 1fe4

Metal transport

PDB id: 1fe4

Contents

Protein chains

68 a.a. *

Ligands

GLC-FRU

IUM

SO4 ×2

Metals

_HG

Waters ×122

* Residue conservation analysis

PDB id:

1fe4

Name:

Metal transport

Title:

Crystal structure of mercury-hah1

Structure:

Copper transport protein atox1. Chain: a, b. Engineered: yes

Source:

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

Resolution:

1.75Å R-factor: 0.204 R-free: 0.218

Authors:

A.K.Wernimont,D.L.Huffman,A.L.Lamb,T.V.O'Halloran,A.C.Rosenzweig

Key ref:

A.K.Wernimont et al. (2000). Structural basis for copper transfer by the metallochaperone for the Menkes/Wilson disease proteins. Nat Struct Biol, 7, 766-771. PubMed id: 10966647 DOI: 10.1038/78999

Date:

20-Jul-00 Release date: 24-Jan-01

Protein chains

O00244  (ATOX1_HUMAN) -  Copper transport protein ATOX1 from Homo sapiens

Seq: 68 a.a.

Struc: 68 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/78999

Nat Struct Biol 7:766-771 (2000)

PubMed id: 10966647

Structural basis for copper transfer by the metallochaperone for the Menkes/Wilson disease proteins.

A.K.Wernimont, D.L.Huffman, A.L.Lamb, T.V.O'Halloran, A.C.Rosenzweig.

ABSTRACT

The Hah1 metallochaperone protein is implicated in copper delivery to the Menkes and Wilson disease proteins. Hah1 and the N-termini of its target proteins belong to a family of metal binding domains characterized by a conserved MT/HCXXC sequence motif. The crystal structure of Hah1 has been determined in the presence of Cu(I), Hg(II), and Cd(II). The 1.8 A resolution structure of CuHah1 reveals a copper ion coordinated by Cys residues from two adjacent Hah1 molecules. The CuHah1 crystal structure is the first of a copper chaperone bound to copper and provides structural support for direct metal ion exchange between conserved MT/HCXXC motifs in two domains. The structures of HgHah1 and CdHah1, determined to 1.75 A resolution, also reveal metal ion coordination by two MT/HCXXC motifs. An extended hydrogen bonding network, unique to the complex of two Hah1 molecules, stabilizes the metal binding sites and suggests specific roles for several conserved residues. Taken together, the structures provide models for intermediates in metal ion transfer and suggest a detailed molecular mechanism for protein recognition and metal ion exchange between MT/HCXXC containing domains.

Selected figure(s)

Figure 1.
Figure 1. Structure of CuHah1. Monomer A is shown in blue and monomer B is shown in yellow. The copper ion is shown as a cyan sphere, and the four Cys residues in the two MT/HCXXC motifs are shown as ball-and-stick representations. a, Stereo view with the noncrystallographic two-fold axis running vertically. b, Viewed 90° from the orientation in (a), looking down the molecular twofold axis.

Figure 3.
Figure 3. Hydrogen bonding interactions. a, Stereo view of the extended hydrogen bonding network at the metal binding site in CuHah1. Monomer A is shown in blue, monomer B is shown in yellow, and the copper ion is shown as a cyan sphere. b, Surface representation of Hah1 color coded according to electrostatic potential: red, -20 kT; white 0 kT; blue, +20 kT. The upper right inset shows the orientation of the two Hah1 molecules. c, Surface representation of a model of Hah1 docked with the Menkes4 domain (PDB accession code 2AW0), color coded as in (b). The Menkes4 domain was superimposed on monomer A of Hah1 to generate the model. In the upper right inset, the Menkes4 domain is shown in magenta and monomer B of Hah1 is shown in yellow.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 766-771) copyright 2000.

Figures were selected by an automated process.