PDBsum entry 2a4h

Oxidoreductase

PDB id: 2a4h

Contents

Protein chain

126 a.a. *

* Residue conservation analysis

PDB id:

2a4h

Name:

Oxidoreductase

Title:

Solution structure of sep15 from drosophila melanogaster

Structure:

Selenoprotein sep15. Chain: a. Fragment: redox domain. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: sep15. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

A.D.Ferguson,V.M.Labunskyy,D.E.Fomenko,Y.Chelliah,C.A.Amezcua,J.Rizo, V.N.Gladyshev,J.Deisenhofer

Key ref:

A.D.Ferguson et al. (2006). NMR Structures of the Selenoproteins Sep15 and SelM Reveal Redox Activity of a New Thioredoxin-like Family. J Biol Chem, 281, 3536-3543. PubMed id: 16319061 DOI: 10.1074/jbc.M511386200

Date:

28-Jun-05 Release date: 13-Dec-05

Protein chain

Q9VVJ7  (Q9VVJ7_DROME) -  Selenoprotein F from Drosophila melanogaster

Seq: 178 a.a.

Struc: 126 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

DOI no: 10.1074/jbc.M511386200

J Biol Chem 281:3536-3543 (2006)

PubMed id: 16319061

NMR Structures of the Selenoproteins Sep15 and SelM Reveal Redox Activity of a New Thioredoxin-like Family.

A.D.Ferguson, V.M.Labunskyy, D.E.Fomenko, D.Araç, Y.Chelliah, C.A.Amezcua, J.Rizo, V.N.Gladyshev, J.Deisenhofer.

ABSTRACT

Selenium has significant health benefits, including potent cancer prevention activity and roles in immune function and the male reproductive system. Selenium-containing proteins, which incorporate this essential micronutrient as selenocysteine, are proposed to mediate the positive effects of dietary selenium. Presented here are the solution NMR structures of the selenoprotein SelM and an ortholog of the selenoprotein Sep15. These data reveal that Sep15 and SelM are structural homologs that establish a new thioredoxin-like protein family. The location of the active-site redox motifs within the fold together with the observed localized conformational changes after thiol-disulfide exchange and measured redox potential indicate that they have redox activity. In mammals, Sep15 expression is regulated by dietary selenium, and either decreased or increased expression of this selenoprotein alters redox homeostasis. A physiological role for Sep15 and SelM as thiol-disulfide oxidoreductases and their contribution to the quality control pathways of the endoplasmic reticulum are discussed.

Selected figure(s)

Figure 1.
Solution NMR structures of SelM and Sep15. A, backbone superposition of the 20 lowest energy structures of SelM (left panel) and Sep15 (right panel). B, ribbon representation of the SelM (left panel) and Sep15 (right panel) structures that are closest to the mean with α-helices colored blue (α1-α3), β-strands colored orange (β1-β4), and coils colored gray. The locations of the redox-active motifs for SelM (CXXU) and Sep15 (CXU) are indicated. Residues 25-34 and residues 121-145 (including an uncleaved C-terminal hexahistidine tag) of SelM are not shown because these regions are flexible. Residues 62-70 (including an uncleaved N-terminal hexahistidine tag) and residues 150-178 of Sep15 are not shown because these regions are also flexible. This figure was prepared with MOLMOL and PyMOL (52).

Figure 2.
Structure-based multiple sequence alignment of SelM and Sep15 homologs. Assigned secondary structure elements for SelM and Sep15 are indicated above each sequence with α-helices colored blue and β-strands colored orange. Strictly conserved residues are shown in blue, and moderately conserved residues are shown in red. The active-site redox motif, including the selenocysteine residue (U), is colored green and is located between the C terminus of strand β1 and the N terminus of helix α1. The following accession numbers were used to generate this alignment: human SelM (27805722); mouse SelM (23956246); zebrafish SelM (29648551); human Sep15 (6094261); mouse Sep15 (20140242); zebrafish Sep15 (68053306); rat Sep15 (20139870); mosquito (18389881); fruit fly Sep15 (24666045). This alignment was produced with 3D-COFFEE (53).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 3536-3543) copyright 2006.

Figures were selected by an automated process.