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PDBsum entry 1kfe
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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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On the role of alphathr183 in the allosteric regulation and catalytic mechanism of tryptophan synthase.
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Authors
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V.Kulik,
M.Weyand,
R.Seidel,
D.Niks,
D.Arac,
M.F.Dunn,
I.Schlichting.
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Ref.
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J Mol Biol, 2002,
324,
677-690.
[DOI no: ]
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PubMed id
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Abstract
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The catalytic activity and substrate channeling of the pyridoxal
5'-phosphate-dependent tryptophan synthase alpha(2)beta(2) complex is regulated
by allosteric interactions that modulate the switching of the enzyme between
open, low activity and closed, high activity states during the catalytic cycle.
The highly conserved alphaThr183 residue is part of loop alphaL6 and is located
next to the alpha-active site and forms part of the alpha-beta subunit
interface. The role of the interactions of alphaThr183 in alpha-site catalysis
and allosteric regulation was investigated by analyzing the kinetics and crystal
structures of the isosteric mutant alphaThr183Val. The mutant displays strongly
impaired allosteric alpha-beta communication, and the catalytic activity of the
alpha-reaction is reduced one hundred fold, whereas the beta-activity is not
affected. The structural work establishes that the basis for the missing
inter-subunit signaling is the lack of loop alphaL6 closure even in the presence
of the alpha-subunit ligands, 3-indolyl-D-glycerol 3'-phosphate, or
3-indolylpropanol 3'-phosphate. The structural basis for the reduced
alpha-activity has its origins in the missing hydrogen bond between alphaThr183
and the catalytic residue, alphaAsp60.
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Figure 7.
Figure 7. SigmaA-weighted 2Fo 2 Fc electron density
maps contoured at 1s around the external aldimine
bLys87 in aT183VSer. The Schiff-base linkage between
PLP and bLys87 is broken. As can be seen from Figure
8, bLys87 interacts with the phosphoryl group of PLP.
The Figure was prepared using ``BOBSCRIPT'',
41
MOLS-
CRIPT
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and RASTER3D.
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The above figure is
reprinted
by permission from Elsevier:
J Mol Biol
(2002,
324,
677-690)
copyright 2002.
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