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PDBsum entry 1pyu
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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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Structural constraints on protein self-Processing in l-Aspartate-Alpha-Decarboxylase.
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Authors
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F.Schmitzberger,
M.L.Kilkenny,
C.M.Lobley,
M.E.Webb,
M.Vinkovic,
D.Matak-Vinkovic,
M.Witty,
D.Y.Chirgadze,
A.G.Smith,
C.Abell,
T.L.Blundell.
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Ref.
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EMBO J, 2003,
22,
6193-6204.
[DOI no: ]
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PubMed id
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Abstract
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Aspartate decarboxylase, which is translated as a pro-protein, undergoes
intramolecular self-cleavage at Gly24-Ser25. We have determined the crystal
structures of an unprocessed native precursor, in addition to Ala24 insertion,
Ala26 insertion and Gly24-->Ser, His11-->Ala, Ser25-->Ala, Ser25-->Cys and
Ser25-->Thr mutants. Comparative analyses of the cleavage site reveal specific
conformational constraints that govern self-processing and demonstrate that
considerable rearrangement must occur. We suggest that Thr57 Ogamma and a water
molecule form an 'oxyanion hole' that likely stabilizes the proposed
oxyoxazolidine intermediate. Thr57 and this water molecule are probable
catalytic residues able to support acid-base catalysis. The conformational
freedom in the loop preceding the cleavage site appears to play a determining
role in the reaction. The molecular mechanism of self-processing, presented
here, emphasizes the importance of stabilization of the oxyoxazolidine
intermediate. Comparison of the structural features shows significant similarity
to those in other self-processing systems, and suggests that models of the
cleavage site of such enzymes based on Ser-->Ala or Ser-->Thr mutants alone may
lead to erroneous interpretations of the mechanism.
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Figure 1.
Figure 1 The ADC tetramer, viewed with the internal four-fold
axis in the plane of the paper, with the secondary structure of
each subunit coloured differently. The pyruvoyl group
(Pvl-group) and Gly24 of one subunit protomer in the foreground
are shown in ball and stick representation (colour scheme as in
Figure 4). Figures 1 and 6 were prepared with Molscript
(Kraulis, 1991) and rendered in Raster3D (Merritt and Bacon,
1997).
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Figure 2.
Figure 2 Schematic representation of the self-processing
reaction, as it is currently understood, applied to ADC. Base 1,
acid 1 and base 2 are designated as :B 1, H-A 1 and :B 2,
respectively.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2003,
22,
6193-6204)
copyright 2003.
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Secondary reference #1
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Title
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Purification and properties of l-Aspartate-Alpha-Decarboxylase, An enzyme that catalyzes the formation of beta-Alanine in escherichia coli.
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Authors
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J.M.Williamson,
G.M.Brown.
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Ref.
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J Biol Chem, 1979,
254,
8074-8082.
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PubMed id
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Secondary reference #2
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Title
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Escherichia coli l-Aspartate-Alpha-Decarboxylase: preprotein processing and observation of reaction intermediates by electrospray mass spectrometry.
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Authors
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M.K.Ramjee,
U.Genschel,
C.Abell,
A.G.Smith.
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Ref.
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Biochem J, 1997,
323,
661-669.
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PubMed id
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Secondary reference #3
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Title
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Crystal structure of aspartate decarboxylase at 2.2 a resolution provides evidence for an ester in protein self-Processing.
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Authors
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A.Albert,
V.Dhanaraj,
U.Genschel,
G.Khan,
M.K.Ramjee,
R.Pulido,
B.L.Sibanda,
F.Von delft,
M.Witty,
T.L.Blundell,
A.G.Smith,
C.Abell.
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Ref.
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Nat Struct Biol, 1998,
5,
289-293.
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PubMed id
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