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PDBsum entry 2a4h
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Oxidoreductase
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PDB id
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2a4h
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References listed in PDB file
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Key reference
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Title
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Nmr structures of the selenoproteins sep15 and selm reveal redox activity of a new thioredoxin-Like family.
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Authors
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A.D.Ferguson,
V.M.Labunskyy,
D.E.Fomenko,
D.Araç,
Y.Chelliah,
C.A.Amezcua,
J.Rizo,
V.N.Gladyshev,
J.Deisenhofer.
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Ref.
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J Biol Chem, 2006,
281,
3536-3543.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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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).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
3536-3543)
copyright 2006.
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