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PDBsum entry 6tim
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Isomerase(intramolecular oxidoreductase)
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PDB id
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6tim
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The adaptability of the active site of trypanosomal triosephosphate isomerase as observed in the crystal structures of three different complexes.
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Authors
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M.E.Noble,
R.K.Wierenga,
A.M.Lambeir,
F.R.Opperdoes,
A.M.Thunnissen,
K.H.Kalk,
H.Groendijk,
W.G.Hol.
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Ref.
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Proteins, 1991,
10,
50-69.
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PubMed id
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Abstract
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Crystals of triosephosphate isomerase from Trypanosoma brucei brucei have been
used in binding studies with three competitive inhibitors of the enzyme's
activity. Highly refined structures have been deduced for the complexes between
trypanosomal triosephosphate isomerase and a substrate analogue
(glycerol-3-phosphate to 2.2 A), a transition state analogue
(3-phosphonopropionic acid to 2.6 A), and a compound structurally related to
both (3-phosphoglycerate to 2.2 A). The active site structures of these
complexes were compared with each other, and with two previously determined
structures of triosephosphate isomerase either free from inhibitor or complexed
with sulfate. The comparison reveals three conformations available to the
"flexible loop" near the active site of triosephosphate isomerase: open (no
ligand), almost closed (sulfate), and fully closed (phosphate/phosphonate
complexes). Also seen to be sensitive to the nature of the active site ligand is
the catalytic residue Glu-167. The side chain of this residue occupies one of
two discrete conformations in each of the structures so far observed. A "swung
out" conformation unsuitable for catalysis is observed when sulfate,
3-phosphoglycerate, or no ligand is bound, while a "swung in" conformation ideal
for catalysis is observed in the complexes with glycerol-3-phosphate or
3-phosphonopropionate. The water structure of the active site is different in
all five structures. The results are discussed with respect to the
triosephosphate isomerase structure function relationship, and with respect to
an on-going drug design project aimed at the selective inhibition of glycolytic
enzymes of T. brucei.
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Secondary reference #1
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Title
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Refined 1.83 a structure of trypanosomal triosephosphate isomerase crystallized in the presence of 2.4 m-Ammonium sulphate. A comparison with the structure of the trypanosomal triosephosphate isomerase-Glycerol-3-Phosphate complex.
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Authors
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R.K.Wierenga,
M.E.Noble,
G.Vriend,
S.Nauche,
W.G.Hol.
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Ref.
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J Mol Biol, 1991,
220,
995.
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PubMed id
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Secondary reference #2
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Title
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The crystal structure of the "open" and the "closed" conformation of the flexible loop of trypanosomal triosephosphate isomerase.
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Authors
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R.K.Wierenga,
M.E.Noble,
J.P.Postma,
H.Groendijk,
K.H.Kalk,
W.G.Hol,
F.R.Opperdoes.
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Ref.
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Proteins, 1991,
10,
33-49.
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PubMed id
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Secondary reference #3
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Title
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Crystallographic and molecular modeling studies on trypanosomal triosephosphate isomerase: a critical assessment of the predicted and observed structures of the complex with 2-Phosphoglycerate.
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Authors
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M.E.Noble,
C.L.Verlinde,
H.Groendijk,
K.H.Kalk,
R.K.Wierenga,
W.G.Hol.
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Ref.
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J Med Chem, 1991,
34,
2709-2718.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Structure determination of the glycosomal triosephosphate isomerase from trypanosoma brucei brucei at 2.4 a resolution.
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Authors
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R.K.Wierenga,
K.H.Kalk,
W.G.Hol.
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Ref.
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J Mol Biol, 1987,
198,
109-121.
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PubMed id
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Secondary reference #5
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Title
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Preliminary crystallographic studies of triosephosphate isomerase from the blood parasite trypanosoma brucei brucei.
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Authors
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R.K.Wierenga,
W.G.Hol,
O.Misset,
F.R.Opperdoes.
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Ref.
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J Mol Biol, 1984,
178,
487-490.
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PubMed id
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