title: Structural basis for the thioredoxin-like activity profile of the glutaredoxin-like NrdH-redoxin from Escherichia coli.
abstract: NrdH-redoxin is a representative of a class of small redox proteins that contain a conserved CXXC motif and are characterized by a glutaredoxin-like amino acid sequence and thioredoxin-like activity profile. The crystal structure of recombinant Escherichia coli NrdH-redoxin in the oxidized state has been determined at 1.7 A resolution by multiwavelength anomalous diffraction. NrdH-redoxin belongs to the thioredoxin superfamily and is structurally most similar to E. coli glutaredoxin 3 and phage T4 glutaredoxin. The angle between the C-terminal helix alpha3 and strand beta4, which differs between thioredoxin and glutaredoxin, has an intermediate value in NrdH-redoxin. The orientation of this helix is to a large extent determined by an extended hydrogen-bond network involving the highly conserved sequence motif (61)WSGFRP(D/E)(67), which is unique to this subclass of the thioredoxin superfamily. Residues that bind glutathione in glutaredoxins are in general not conserved in NrdH-redoxin, and no glutathione-binding cleft is present. Instead, NrdH-redoxin contains a wide hydrophobic pocket at the surface, similar to thioredoxin. Modeling studies suggest that NrdH-redoxin can interact with E. coli thioredoxin reductase at this pocket and also via a loop that is complementary to a crevice in the reductase in a similar manner as observed in the E. coli thioredoxin-thioredoxin reductase complex.
authors: Division of Molecular Structural Biology and the Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, S-171 77 Sweden.
authors: M
authors: M
authors: Stehr
authors: G
authors: G
authors: Schneider
authors: F
authors: F
authors: Aslund
authors: A
authors: A
authors: Holmgren
authors: Y
authors: Y
authors: Lindqvist
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D054477:Glutaredoxins; C107179:NrdH protein, E Coli; D011506:Proteins; D011994:Recombinant Proteins; D013879:Thioredoxins; D010088:Oxidoreductases; D005978:Glutathione