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PDBsum entry 2vbg
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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 of the branched-Chain keto acid decarboxylase (kdca) from lactococcus lactis provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction.
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Authors
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C.L.Berthold,
D.Gocke,
M.D.Wood,
F.J.Leeper,
M.Pohl,
G.Schneider.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2007,
63,
1217-1224.
[DOI no: ]
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PubMed id
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Abstract
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The thiamin diphosphate (ThDP) dependent branched-chain keto acid decarboxylase
(KdcA) from Lactococcus lactis catalyzes the decarboxylation of
3-methyl-2-oxobutanoic acid to 3-methylpropanal (isobutyraldehyde) and CO2. The
enzyme is also able to catalyze carboligation reactions with an exceptionally
broad substrate range, a feature that makes KdcA a potentially valuable
biocatalyst for C-C bond formation, in particular for the enzymatic synthesis of
diversely substituted 2-hydroxyketones with high enantioselectivity. The crystal
structures of recombinant holo-KdcA and of a complex with an inhibitory ThDP
analogue mimicking a reaction intermediate have been determined to resolutions
of 1.6 and 1.8 A, respectively. KdcA shows the fold and cofactor-protein
interactions typical of thiamin-dependent enzymes. In contrast to the tetrameric
assembly displayed by most other ThDP-dependent decarboxylases of known
structure, KdcA is a homodimer. The crystal structures provide insights into the
structural basis of substrate selectivity and stereoselectivity of the enzyme
and thus are suitable as a framework for the redesign of the substrate profile
in carboligation reactions.
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Figure 2.
Figure 2 A schematic representation of the S-pocket. (a) When
there is no S-pocket or an S-pocket that is too small to fit the
acceptor substrate side chain R, it will bind with the Si face
towards the enamine and the (R)-enantiomer will be formed. (b)
Perfect fit of the acceptor substrate side chain in the S-pocket
above the thiazolium ring will allow the substrate to align,
resulting in the (S)-enantiomer.
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Figure 8.
Figure 8 Benzaldehyde modelled as acyl donor aldehyde
covalently bound to ThDP in the form of the enamine (grey) and
as acceptor substrate (blue) with the Si side facing the enamine.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2007,
63,
1217-1224)
copyright 2007.
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