PDBsum entry 2hzf

Electron transport, oxidoreductase

PDB id: 2hzf

Contents

Protein chains

110 a.a.

Waters ×148

References listed in PDB file

Key reference

Title

Crystal structures of a poxviral glutaredoxin in the oxidized and reduced states show redox-Correlated structural changes.

Authors

J.P.Bacik, B.Hazes.

Ref.

J Mol Biol, 2007, 365, 1545-1558. [DOI no: 10.1016/j.jmb.2006.11.002]

PubMed id

17137595

Abstract

Glutaredoxins act as reducing agents for the large subunit of ribonucleotide reductase (R1) in many prokaryotes and eukaryotes, including humans. The same relationship has been proposed for the glutaredoxin and R1 proteins expressed by all orthopoxviruses, including vaccinia, variola, and ectromelia virus. Interestingly, the orthopoxviral proteins share 45% and 78% sequence identity with human glutaredoxin-1 (Grx-1) and R1, respectively. To study structure-function relationships of the vertebrate Grx-1 family, and reveal potential viral adaptations, we have determined crystal structures of the ectromelia virus glutaredoxin, EVM053, in the oxidized and reduced states. The structures show a large redox-induced conformational rearrangement of Tyr21 and Thr22 near the active site. We predict that the movement of Tyr21 is a viral-specific adaptation that increases the redox potential by stabilizing the reduced state. The conformational switch of Thr22 appears to be shared by vertebrate Grx-1 and may affect the strictly conserved Lys20. A crystal packing-induced structural change in residues 68-70 affects the GSH-binding loop, and our structures reveal a potential interaction network that connects the GSH-binding loop and the active site. EVM053 also exhibits a novel cis-proline (Pro53) in a loop that has been shown to contribute to R1-binding in Escherichia coli Grx-1. The cis-peptide bond of Pro53 may be required to promote electrostatic interactions between Lys52 and the C-terminal carboxylate of R1. Finally, dimethylarsenite was covalently attached to Cys23 in one reduced EVM053 structure and our preliminary data show that EVM053 has dimethylarsenate reductase activity.

Figure 1.
Figure 1. Cartoon representation of EVM053 in the oxidized conformation. Helices are shown as coils and strands as arrows. The disulfide bond formed by the active site cysteine residues is shown in orange and the cis-Pro53 is drawn in ball-and-stick format. This Figure was generated using MOLSCRIPT^67 and Raster3D.^68

Figure 2.
Figure 2. Electron density (2|F[obs]|–|F[calc]|) for the active site of EVM053 in the (a) oxidized; (b) reduced; (c) dimethylarsenylated states. The disulfide bond in the oxidized structure and the proposed hydrogen bond in the reduced structure are indicated by broken lines. This Figure was generated using Xfit^65 and Raster3D.^68

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 365, 1545-1558) copyright 2007.