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PDBsum entry 1b6t
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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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The crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity.
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Authors
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T.Izard,
A.Geerlof.
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Ref.
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EMBO J, 1999,
18,
2021-2030.
[DOI no: ]
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PubMed id
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Abstract
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Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in bacteria
that catalyses a rate-limiting step in coenzyme A (CoA) biosynthesis, by
transferring an adenylyl group from ATP to 4'-phosphopantetheine, yielding
dephospho-CoA (dPCoA). Each phosphopantetheine adenylyltransferase (PPAT)
subunit displays a dinucleotide-binding fold that is structurally similar to
that in class I aminoacyl-tRNA synthetases. Superposition of bound adenylyl
moieties from dPCoA in PPAT and ATP in aminoacyl-tRNA synthetases suggests
nucleophilic attack by the 4'-phosphopantetheine on the alpha-phosphate of ATP.
The proposed catalytic mechanism implicates transition state stabilization by
PPAT without involving functional groups of the enzyme in a chemical sense in
the reaction. The crystal structure of the enzyme from Escherichia coli in
complex with dPCoA shows that binding at one site causes a vice-like movement of
active site residues lining the active site surface. The mode of enzyme product
formation is highly concerted, with only one trimer of the PPAT hexamer showing
evidence of dPCoA binding. The homologous active site attachment of ATP and the
structural distribution of predicted sequence-binding motifs in PPAT classify
the enzyme as belonging to the nucleotidyltransferase superfamily.
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Figure 1.
Figure 1 The penultimate step in the CoA biosynthetic pathway.
PPAT reversibly catalyses the adenylation by ATP of
4'-phosphopantetheine, forming 3'-dephospho-CoA and
pyrophosphate.
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Figure 3.
Figure 3 The PPAT hexamer. (A) Electrostatic surface potential
(using the program GRASP; Nicholls et al., 1991) of the PPAT
hexamer along the triad (red, negative; blue, positive; white,
uncharged). The diameter along the 3-fold axis is  75
Å, with a channel across the entire hexamer with a
diameter of at least 10 Å. The substrates and products
must enter through this cavity to bind to the active site of the
protein. Space-filling representations (using the program
RASTER3D; Bacon and Anderson, 1988; Merritt and Murphy, 1994)
looking down (B) the triad and (C) the dyad. Each of the six
subunits is coloured differently.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
2021-2030)
copyright 1999.
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