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PDBsum entry 1q7c
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Oxidoreductase
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PDB id
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1q7c
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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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Cofactor-Induced conformational rearrangements establish a catalytically competent active site and a proton relay conduit in fabg.
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Authors
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A.C.Price,
Y.M.Zhang,
C.O.Rock,
S.W.White.
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Ref.
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Structure, 2004,
12,
417-428.
[DOI no: ]
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PubMed id
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Abstract
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beta-Ketoacyl-acyl carrier protein reductase (FabG) is a key component in the
type II fatty acid synthase system. The structures of Escherichia coli FabG and
mutant in binary complexes with NADP(H) reveal that
mechanistically important conformational changes accompany cofactor binding. The
active site Ser-Tyr-Lys triad is repositioned into a catalytically competent
constellation, and a hydrogen bonded network consisting of ribose hydroxyls, the
Ser-Tyr-Lys triad, and four water molecules creates a proton wire to replenish
the tyrosine proton donated during catalysis. Also, a disordered loop in FabG
forms a substructure in the complex that shapes the entrance to the active site.
A key observation is that the nicotinamide portion of the cofactor is disordered
in the FabG[Y151F].NADP(H) complex, and Tyr151 appears to be necessary for
is
defective in NADPH binding. Finally, structural changes consistent with the
observed negative cooperativity of FabG are described.
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Figure 5.
Figure 5. Structural Rearrangements Explain the Allosteric
Behavior of FabG
In the two panels, the α helices of
monomer A are orange, the β strands and coils of monomer A are
yellow, the α helices of monomer B are blue, and the β strands
and coils of monomer B are green.
(A) A close up of the
FabG intermonomer interface at region “c” as defined in
Figure 1B. Glu168′ from one monomer forms hydrogen bonds to
the amide nitrogens of Leu95 and Met96 on the adjacent monomer,
and residues N-terminal to Gly147 on the β5-α5 loop are
disordered.
(B) A close up of the same region in the
FabG·NADP^+ complex. Note that Glu168′ has shifted its
hydrogen bond register to the amide nitrogens of Leu95 and
Gly147, and the residues N-terminal to Gly147 on the β5-α5
loop are now ordered. The figure was produced using MOLSCRIPT
(Kraulis, 1991) and rendered with RASTER3D (Merritt and Murphy,
1994).
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Figure 8.
Figure 8. An Overview of the Interacting Monomers in the
FabG·NADP^+ Complex
Glu168′ and its hydrogen
bonding interactions, as depicted in Figure 5B, are shown at the
interface. Shown in monomer A are the bound cofactor, the active
site residues, the ordered β5-α5 loop (purple), and Asn145,
which we propose may interact with the incoming pantetheine
moiety of the ACP-bound substrate. Shown in monomer B are
Arg129′ and Arg172′, which interact with the incoming ACP
(Zhang et al., 2003b). The figure was produced using MOLSCRIPT
(Kraulis, 1991) and rendered with RASTER3D (Merritt and Murphy,
1994).
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2004,
12,
417-428)
copyright 2004.
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