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PDBsum entry 2on7
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Structure of nagst-1
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Structure:
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Na glutathione s-transferase 1. Chain: a, b, c, d. Synonym: nagst-1. Engineered: yes
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Source:
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Necator americanus. Organism_taxid: 51031. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
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Resolution:
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2.40Å
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R-factor:
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0.194
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R-free:
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0.284
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Authors:
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O.A.Asojo,M.Ngamelue,H.Homma,G.Goud,B.Zhan,P.J.Hotez
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Key ref:
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O.A.Asojo
et al.
(2007).
X-ray structures of Na-GST-1 and Na-GST-2 two glutathione S-transferase from the human hookworm Necator americanus.
Bmc Struct Biol,
7,
42.
PubMed id:
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Date:
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23-Jan-07
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Release date:
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07-Aug-07
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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Key: |
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Secondary structure |
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CATH domain |
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Bmc Struct Biol
7:42
(2007)
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PubMed id:
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X-ray structures of Na-GST-1 and Na-GST-2 two glutathione S-transferase from the human hookworm Necator americanus.
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O.A.Asojo,
K.Homma,
M.Sedlacek,
M.Ngamelue,
G.N.Goud,
B.Zhan,
V.Deumic,
O.Asojo,
P.J.Hotez.
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ABSTRACT
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BACKGROUND: Human hookworm infection is a major cause of anemia and malnutrition
of adults and children in the developing world. As part of on-going efforts to
control hookworm infection, The Human Hookworm Vaccine Initiative has identified
candidate vaccine antigens from the infective L3 larval stages and adult stages
of the parasite. Adult stage antigens include the cytosolic
glutathione-S-transferases (GSTs). Nematode GSTs facilitate the inactivation and
degradation of a variety of electrophilic substrates (drugs) via the
nucleophilic addition of reduced glutathione. Parasite GSTs also play
significant roles in multi-drug resistance and the modulation of host-immune
defense mechanisms. RESULTS: The crystal structures of Na-GST-1 and Na-GST-2,
two major GSTs from Necator americanus the main human hookworm parasite, have
been solved at the resolution limits of 2.4 A and 1.9 A respectively. The
structure of Na-GST-1 was refined to R-factor 18.9% (R-free 28.3%) while that of
Na-GST-2 was refined to R-factor 17.1% (R-free 21.7%). Glutathione usurped
during the fermentation process in bound in the glutathione binding site
(G-site) of each monomer of Na-GST-2. Na-GST-1 is uncomplexed and its G-site is
abrogated by Gln 50. These first structures of human hookworm parasite GSTs
could aid the design of novel hookworm drugs. CONCLUSION: The 3-dimensional
structures of Na-GST-1 and Na-GST-2 show two views of human hookworm GSTs. While
the GST-complex structure of Na-GST-2 reveals a typical GST G-site that of
Na-GST-1 suggests that there is some conformational flexibility required in
order to bind the substrate GST. In addition, the overall binding cavities for
both are larger, more open, as well as more accessible to diverse ligands than
those of GSTs from organisms that have other major detoxifying mechanisms. The
results from this study could aid in the design of novel drugs and vaccine
antigens.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.M.Bethony,
R.N.Cole,
X.Guo,
S.Kamhawi,
M.W.Lightowlers,
A.Loukas,
W.Petri,
S.Reed,
J.G.Valenzuela,
and
P.J.Hotez
(2011).
Vaccines to combat the neglected tropical diseases.
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Immunol Rev,
239,
237-270.
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A.R.Jariwala,
L.M.Oliveira,
D.J.Diemert,
B.Keegan,
J.L.Plieskatt,
M.V.Periago,
M.E.Bottazzi,
P.J.Hotez,
and
J.M.Bethony
(2010).
Potency testing for the experimental Na-GST-1 hookworm vaccine.
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Expert Rev Vaccines,
9,
1219-1230.
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B.Zhan,
S.Perally,
P.M.Brophy,
J.Xue,
G.Goud,
S.Liu,
V.Deumic,
L.M.de Oliveira,
J.Bethony,
M.E.Bottazzi,
D.Jiang,
P.Gillespie,
S.H.Xiao,
R.Gupta,
A.Loukas,
N.Ranjit,
S.Lustigman,
Y.Oksov,
and
P.Hotez
(2010).
Molecular cloning, biochemical characterization, and partial protective immunity of the heme-binding glutathione S-transferases from the human hookworm Necator americanus.
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Infect Immun,
78,
1552-1563.
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M.O.Harhay,
J.Horton,
and
P.L.Olliaro
(2010).
Epidemiology and control of human gastrointestinal parasites in children.
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Expert Rev Anti Infect Ther,
8,
219-234.
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P.J.Hotez,
J.M.Bethony,
D.J.Diemert,
M.Pearson,
and
A.Loukas
(2010).
Developing vaccines to combat hookworm infection and intestinal schistosomiasis.
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Nat Rev Microbiol,
8,
814-826.
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M.J.Smout,
T.Laha,
J.Mulvenna,
B.Sripa,
S.Suttiprapa,
A.Jones,
P.J.Brindley,
and
A.Loukas
(2009).
A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells.
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PLoS Pathog,
5,
e1000611.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
