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PDBsum entry 2o2c
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References listed in PDB file
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Key reference
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Title
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Crystal structure of phosphoglucose isomerase from trypanosoma brucei complexed with glucose-6-Phosphate at 1.6 a resolution.
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Authors
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D.Arsenieva,
B.L.Appavu,
G.H.Mazock,
C.J.Jeffery.
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Ref.
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Proteins, 2008,
74,
72-80.
[DOI no: ]
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PubMed id
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Abstract
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Enzymes of glycolysis in Trypanosoma brucei have been identified as potential
drug targets for African sleeping sickness because glycolysis is the only source
of ATP for the bloodstream form of this parasite. Several inhibitors were
previously reported to bind preferentially to trypanosomal phosphoglucose
isomerase (PGI, the second enzyme in glycolysis) than to mammalian PGIs, which
suggests that PGI might make a good target for species-specific drug design.
Herein, we report recombinant expression, purification, crystallization and
X-ray crystal structure determination of T. brucei PGI. One structure solved at
1.6 A resolution contains a substrate, D-glucose-6-phosphate, in an extended
conformation in the active site. A second structure solved at 1.9 A resolution
contains a citrate molecule in the active site. The structures are compared with
the crystal structures of PGI from humans and from Leishmania mexicana. The
availability of recombinant tPGI and its first high-resolution crystal
structures are initial steps in considering this enzyme as a potential drug
target. Proteins 2009. (c) 2008 Wiley-Liss, Inc.
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Figure 2.
Figure 2. Overall structure of a dimer of tPGI with bound G6P.
One subunit is shown in color, the other subunit is in black and
gray. The ordered fragment of the N-terminal extension (green,
amino acids 43-46), the large domain (yellow, amino acids 47-197
and 318-562), the small domain (purple, amino acids 198-317),
and the C-terminal segment (light purple, amino acids 563-606)
are shown. Molecules of G6P are represented by red
ball-and-stick models and indicate the locations of the active
sites.
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Figure 4.
Figure 4. Superposed active sites of the tPGI/G6P (black) and
hPGI/5PAA (PDB code 1NUH, white) enzyme/ligand complexes. All
atoms of amino acid residues 206-208, 259-263, Gly325, Arg326,
and Gln407 of subunit A and His442, Gln564 and the backbone
atoms of Glu411 of subunit B of tPGI were superposed onto the
corresponding atoms of hPGI (subunit A of 1NUH).
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2008,
74,
72-80)
copyright 2008.
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