Sam Pletz '13 and
Jimmy Chapman '13
peroxidase belongs to the
selenoprotein family and is observed in mammals, birds, and fish. This
enzyme along with other members of the selenoprotein family have an
integral role in the defense mechanisms of these organisms.
Glutathione Peroxidase from
bovine plasma plays a role in catalyzing the reduction of
hydroperoxides. This enzyme also protects biomembranes and cell
structures from oxidative damage. Glutathione
Peroxidase accomplishes this
through the reduction of lipid hydroperoxides to their corresponding
alcohols and through the reduction of free hydrogen peroxide to water
using glutathione as the reducing substrate. The enzyme reduces lipid
hydroperoxidases and hydrogen peroxide through the following proposed
+ 2GSH → ROH + H2O + GSSG
crystal structure of Seleno-Glutathione
Peroxidase from human plasma has
been characterized and differs only slightly from that of Glutathione
Peroxidase from bovine plasma
(Rin et al. 1997). However, the physilogical role of Glutathione
Peroxidase in humans is still
unclear because of the low levels of reduced glutathione and the low
reactivity of the enzyme (Rin et al. 1997).
peroxidase is a tetramer consisting of 4 identical single polypeptide
chains each with 178 amino acid residues
monomer contains two
parallel and two anti-parallel pleated β-sheets
α helices 1,
exist on one side of the β
sheet complex whereas
exists on the other side
active selenocysteine is
located near the first turn of α1
region of the monomer consists of α3 and two anti-parallel
and several β turns. Hydrogen
bonding between β1 and β3 stabilizes and completes
the four stranded β complex.
unique feature of the
protein is the tetrahedral quaternary
that is a planar arrangement of four identical monomers
The contact regions of
each subunit to another consists of 16 amino acid residues; both polar
and non-polar amino acid residues can be found between them.
hydrogen bonds can also be formed across the local axis by residues Glu-77,
and the symmetry equivalent pair, Glu-277
(Epp et al. 1983). Therefore, each monomer has 20 identical
interactions with each other.
side chains and other backbone
atoms contribute to more subunit contacts between each monomer. The
interactions between each monomer decrease the accessible surface area
and is the main source of free energy keeping the monomers together
(Epp et al. 1983). Because each monomer is chemically identical, one
would predict roughly identical values of the individual binding
constants between the GSH peroxidase monomers (Epp et al. 1983).
peroxidase has high reaction rates. The reason for this is that the
catalytically active selenocysteine residues
on the molecular
are exposed which allows for easy access for substrates
allow for hydrogen bonding with the selenocysteine
to stabilize the active-site.
in the area where the carboxy ends of two
and the N-terminal end of one Alpha-helix
This is the area where
substrate binding occurs.The
alpha1 helix combined
with two adjacent parallel Beta strands form a Beta-Alpha-Beta
Thus secondary structure
formation is favorable
due to the carboxy ends
of the Beta strands near the binding region.
The macrodipole created by alignment of the alpha helix parallel to the
helix axis stabilizes the active-site selenolate.
cyanide, the charge distribution at the active site is shifted. The
seleno-amino acid has a negative charge taken away.
This results in a 0.4-nm shift of the Met-101
opposite surface of the monomer compared to the selenium
The shift is consistent with the formation of hydrogen bonds of the
selenoloate to 148-Trp
and to 70-Gln N.
This results in stabilization
of the active-site
oxidized Gluthatione peroxidase binds the donor substrate
high affinity (Ren
et al. 1983). In contrast, reduced
GSH peroxidase binds glutathione with low affinity. In an oxidized
environment, GSH peroxidase binds four glutathione molecules per
subunit by a selenosulfide linkage. The specific binding interaction
between a subunit of the enzyme and glutathione can be characterized by
several important amino acid interactions. Amino acids Arg-40
form a salt bridge with the glutathione
et al. 1997).
forms a hydrogen bond with the N-terminus of the ligand
et al. 1997).
Epp Otto, Ladenstein Rudolf, and Wendel
The Refined Structure of the Selenoenzyme Glutathione Peroxidase at
0.2-nm Resolution. Biochemistry
Ladenstein Rudolf, Epp Otto, Bartels Klaus,
Jones Alwyn, Huber Robert and Wendel Albrecht.
Structure Analysis and Molecular Model of the Selenoenzyme Glutathione
Peroxidase at 2.8 Angstrom Resolution. Journal
of Molecular Biology
Bin, Huang Wenhu, Akesson Bjorn, Ladenstein
The Crystal Structure of Seleno-Glutathione Peroxidase from Human
Plasma at 2.9 A Resolution. Journal
of Molecular Biology
C. K., Purushotham B., Radhakrishna M.P., Abhilekha
M.P., and Vagdevi M.H.
Role of Selenium in Pets Health and Nutrition: A Review. Asian
of Animal Sciences