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PDBsum entry 2ghi
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Transport protein
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PDB id
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2ghi
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References listed in PDB file
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Key reference
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Title
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Genome-Scale protein expression and structural biology of plasmodium falciparum and related apicomplexan organisms.
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Authors
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M.Vedadi,
J.Lew,
J.Artz,
M.Amani,
Y.Zhao,
A.Dong,
G.A.Wasney,
M.Gao,
T.Hills,
S.Brokx,
W.Qiu,
S.Sharma,
A.Diassiti,
Z.Alam,
M.Melone,
A.Mulichak,
A.Wernimont,
J.Bray,
P.Loppnau,
O.Plotnikova,
K.Newberry,
E.Sundararajan,
S.Houston,
J.Walker,
W.Tempel,
A.Bochkarev,
I.Kozieradzki,
A.Edwards,
C.Arrowsmith,
D.Roos,
K.Kain,
R.Hui.
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Ref.
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Mol Biochem Parasitol, 2007,
151,
100-110.
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PubMed id
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Abstract
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Parasites from the protozoan phylum Apicomplexa are responsible for diseases,
such as malaria, toxoplasmosis and cryptosporidiosis, all of which have
significantly higher rates of mortality and morbidity in economically
underdeveloped regions of the world. Advances in vaccine development and drug
discovery are urgently needed to control these diseases and can be facilitated
by production of purified recombinant proteins from Apicomplexan genomes and
determination of their 3D structures. To date, both heterologous expression and
crystallization of Apicomplexan proteins have seen only limited success. In an
effort to explore the effectiveness of producing and crystallizing proteins on a
genome-scale using a standardized methodology, over 400 distinct Plasmodium
falciparum target genes were chosen representing different cellular classes,
along with select orthologues from four other Plasmodium species as well as
Cryptosporidium parvum and Toxoplasma gondii. From a total of 1008 genes from
the seven genomes, 304 (30.2%) produced purified soluble proteins and 97 (9.6%)
crystallized, culminating in 36 crystal structures. These results demonstrate
that, contrary to previous findings, a standardized platform using Escherichia
coli can be effective for genome-scale production and crystallography of
Apicomplexan proteins. Predictably, orthologous proteins from different
Apicomplexan genomes behaved differently in expression, purification and
crystallization, although the overall success rates of Plasmodium orthologues do
not differ significantly. Their differences were effectively exploited to
elevate the overall productivity to levels comparable to the most successful
ongoing structural genomics projects: 229 of the 468 target genes produced
purified soluble protein from one or more organisms, with 80 and 32 of the
purified targets, respectively, leading to crystals and ultimately structures
from one or more orthologues.
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