PDBsum entry 2v6o

Oxidoreductase

PDB id: 2v6o

Contents

Protein chain

586 a.a. *

Ligands

FAD

PG4 ×4

NO3

Waters ×312

* Residue conservation analysis

PDB id:

2v6o

Name:

Oxidoreductase

Title:

Structure of schistosoma mansoni thioredoxin-glutathione reductase (smtgr)

Structure:

Thioredoxin glutathione reductase. Chain: a. Fragment: residues 1-596. Engineered: yes. Other_details: fad cofactor bound

Source:

Schistosoma mansoni. Blood fluke. Organism_taxid: 6183. Expressed in: escherichia coli. Expression_system_taxid: 469008. Other_details: adult cdna

Resolution:

2.20Å R-factor: 0.191 R-free: 0.252

Authors:

A.E.Miele,F.Angelucci,G.Boumis,D.Dimastrogiovanni,A.Bellelli, M.Brunori

Key ref:

F.Angelucci et al. (2008). Glutathione reductase and thioredoxin reductase at the crossroad: the structure of Schistosoma mansoni thioredoxin glutathione reductase. Proteins, 72, 936-945. PubMed id: 18300227 DOI: 10.1002/prot.21986

Date:

19-Jul-07 Release date: 04-Mar-08

Protein chain

Q962Y6  (Q962Y6_SCHMA) -  thioredoxin-disulfide reductase from Schistosoma mansoni

Seq: 598 a.a.

Struc: 586 a.a.

Enzyme reactions

• Enzyme class: E.C.1.8.1.9 - thioredoxin-disulfide reductase (NADPH).
• Reaction: [thioredoxin]-dithiol + NADP⁺ = [thioredoxin]-disulfide + NADPH + H⁺

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

Added reference

DOI no: 10.1002/prot.21986

Proteins 72:936-945 (2008)

PubMed id: 18300227

Glutathione reductase and thioredoxin reductase at the crossroad: the structure of Schistosoma mansoni thioredoxin glutathione reductase.

F.Angelucci, A.E.Miele, G.Boumis, D.Dimastrogiovanni, M.Brunori, A.Bellelli.

ABSTRACT

Thioredoxin glutathione reductase (TGR) is a key flavoenzyme expressed by schistosomes that bridges two detoxification pathways crucial for the parasite survival in the host's organism. In this article we report the crystal structure (at 2.2 A resolution) of TGR from Schistosoma mansoni (SmTGR), deleted in the last two residues. The structure reveals the peculiar architecture of this chimeric enzyme: the small Glutaredoxin (Grx) domain at the N-terminus is joined to the large thioredoxin reductase (TR) one via an extended complementary surface, involving residues not conserved in the Grx superfamily; the TR domain interacts with an identical partner via its C-terminal domain, forming a dimer with a twisted "W" shape. Although lacking the penultimate Selenocysteine residue (Sec), the enzyme is still able to reduce oxidized glutathione. These data update the interpretation of the interdomain communication in TGR enzymes. The possible function of this enzyme in pathogenic parasites is discussed.

Selected figure(s)

Figure 1.
Figure 1. The structure of truncated Schistosoma mansoni TGR in ribbon representation, produced with CCP4MG.[23] Panel A: Overall structural organization of the biological unit of the enzyme: the W-shaped SmTGR dimer. One monomer is in blue and the other monomer is colored according to the division in domains from N- to C- terminus: Grx domain in light blue (1-107); FAD binding domain in gold (108-257 and 391-461); NADPH binding domain in green (258-358 and 364-390); the interface domain in magenta (462-493). The linker regions between Grx and TR (103-107) domains in magenta and the insertion (359-363) peculiar to SmTGRs in red lie at the top and at the bottom, respectively. Panel B: as in A, the view is from the top, looking down the twofold dimerization axis (in black for clarity). Panel C: The FAD binding site. View of the 2Fo-Fc electron density map around the FAD cofactor contoured at 1.0 . The backbone of SmTGR around the active site is in ribbon, the residues (K162 and Y296) that stabilize the position of the flavine ring, together with the catalytic disulphide (C154-C159), packing the isoalloxazine ring of the FAD, are shown in sticks. Residues from the symmetrical monomer B, which are implicated in the catalytic active site (H571B and E576B) are also shown. Distances of the H-bond network range from 2.7 to 3.4 Å.

Figure 2.
Figure 2. The putative orientation of NADPH and GSSG in SmTGR. The SmTGR dimer is shown in a same orientation as in Figure 1(B), and is superimposed to hGR (olive-green) and hTR1 (grey). For clarity the superimposition is displayed only for one monomer. NADPH and GSSG from the superposed structures are showed in CPK. Color coding as in Figure 1.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 72, 936-945) copyright 2008.

Figures were selected by the author.