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PDBsum entry 1br5
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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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Structure-Based identification of a ricin inhibitor.
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Authors
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X.Yan,
T.Hollis,
M.Svinth,
P.Day,
A.F.Monzingo,
G.W.Milne,
J.D.Robertus.
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Ref.
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J Mol Biol, 1997,
266,
1043-1049.
[DOI no: ]
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PubMed id
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Abstract
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Ricin is a potent cytotoxin which has been used widely in the construction of
therapeutic agents such as immunotoxins. Recently it has been used by
governments and underground groups as a poison. There is interest in identifying
and designing effective inhibitors of the ricin A chain (RTA). In this study
computer-assisted searches indicated that pterins might bind in the RTA active
site which normally recognizes a specific adenine base on rRNA. Kinetic assays
showed that pteroic acid could inhibit RTA activity with an apparent Ki of 0.6
mM. A 2.3 A crystal structure of the complex revealed the mode of binding. The
pterin ring displaces Tyr80 and binds in the adenine pocket making specific
hydrogen bonds to active site residues. The benzoate moiety of pteroic acid
binds on the opposite side of Tyr80 making van der Waals contact with the Tyr
ring and forming a hydrogen bond with Asn78. Neopterin, a propane triol
derivative of pterin, also binds to RTA as revealed by the X-ray structure of
its complex with RTA. Neither pterin-6-carboxylic acid nor folic acid bind to
the crystal or act as inhibitors. The models observed suggest alterations to the
pterin moiety which may produce more potent and specific RTA inhibitors.
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Figure 3.
Figure 3. Interactions between pteroic acid and RTA.
Hydrogen bonds are shown as broken lines with the lengths
indicated.
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Figure 5.
Figure 5. Binding of neopterin in the RTA active site.
Hydrogen bonds are shown as broken lines and the lengths are
indicated.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
266,
1043-1049)
copyright 1997.
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Secondary reference #1
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Title
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Structure of recombinant ricin a chain at 2.3 a.
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Authors
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D.Mlsna,
A.F.Monzingo,
B.J.Katzin,
S.Ernst,
J.D.Robertus.
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Ref.
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Protein Sci, 1993,
2,
429-435.
[DOI no: ]
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PubMed id
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Figure 2.
Fig. 2. Superposition of the refined
models of ricin Aand rRTA. Recom-
binant RTA, as refinedin this study is
shown in the heavy ondsasa Ca
trace. The refined ricin A chain (Ru-
tenber et al., 1991) is shown in thin
bonds.
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Figure 5.
Fig. 5. The active site of ricin. The conforma-
of ricin A is shown in light bonds and that
f rRTA n heavy bonds.
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The above figures are
reproduced from the cited reference
which is an Open Access publication published by the Protein Society
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Secondary reference #2
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Title
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Structure of ricin a-Chain at 2.5 a.
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Authors
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B.J.Katzin,
E.J.Collins,
J.D.Robertus.
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Ref.
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Proteins, 1991,
10,
251-259.
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PubMed id
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