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PDBsum entry 1c9d
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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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Crystallographic studies of phosphonate-Based alpha-Reaction transition-State analogues complexed to tryptophan synthase.
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Authors
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A.Sachpatzidis,
C.Dealwis,
J.B.Lubetsky,
P.H.Liang,
K.S.Anderson,
E.Lolis.
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Ref.
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Biochemistry, 1999,
38,
12665-12674.
[DOI no: ]
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PubMed id
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Abstract
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In an effort to use a structure-based approach for the design of new herbicides,
the crystal structures of complexes of tryptophan synthase with a series of
phosphonate enzyme inhibitors were determined at 2.3 A or higher resolution.
These inhibitors were designed to mimic the transition state formed during the
alpha-reaction of the enzyme and, as expected, have affinities much greater than
that of the natural substrate indole-3-glycerol phosphate or its nonhydrolyzable
analogue indole propanol phosphate (IPP). These inhibitors are ortho-substituted
arylthioalkylphosphonate derivatives that have an sp(3)-hybridized sulfur atom,
designed to mimic the putative tetrahedral transition state at the C3 atom of
the indole, and lack the C2 atom to allow for higher conformational flexibility.
Overall, the inhibitors bind in a fashion similar to that of IPP. Glu-49 and
Phe-212 are the two active site residues whose conformation changes upon
inhibitor binding. A very short hydrogen bond between a phosphonate oxygen and
the Ser-235 hydroxyl oxygen may be responsible for stabilization of the
enzyme-inhibitor complexes. Implications for the mechanism of catalysis as well
as directions for more potent inhibitors are discussed.
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Secondary reference #1
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Title
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Three-Dimensional structure of the tryptophan synthase alpha 2 beta 2 multienzyme complex from salmonella typhimurium.
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Authors
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C.C.Hyde,
S.A.Ahmed,
E.A.Padlan,
E.W.Miles,
D.R.Davies.
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Ref.
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J Biol Chem, 1988,
263,
17857-17871.
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PubMed id
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Secondary reference #2
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Title
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Loop closure and intersubunit communication in tryptophan synthase.
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Authors
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T.R.Schneider,
E.Gerhardt,
M.Lee,
P.H.Liang,
K.S.Anderson,
I.Schlichting.
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Ref.
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Biochemistry, 1998,
37,
5394-5406.
[DOI no: ]
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PubMed id
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