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PDBsum entry 1f91
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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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Structures of beta-Ketoacyl-Acyl carrier protein synthase i complexed with fatty acids elucidate its catalytic machinery.
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Authors
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J.G.Olsen,
A.Kadziola,
P.Von wettstein-Knowles,
M.Siggaard-Andersen,
S.Larsen.
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Ref.
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Structure, 2001,
9,
233-243.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: beta-ketoacyl-acyl carrier protein synthase (KAS) I is vital for the
construction of the unsaturated fatty acid carbon skeletons characterizing E.
coli membrane lipids. The new carbon-carbon bonds are created by KAS I in a
Claisen condensation performed in a three-step enzymatic reaction. KAS I belongs
to the thiolase fold enzymes, of which structures are known for five other
enzymes. RESULTS: Structures of the catalytic Cys-Ser KAS I mutant with
covalently bound C10 and C12 acyl substrates have been determined to 2.40 and
1.85 A resolution, respectively. The KAS I dimer is not changed by the formation
of the complexes but reveals an asymmetric binding of the two substrates bound
to the dimer. A detailed model is proposed for the catalysis of KAS I. Of the
two histidines required for decarboxylation, one donates a hydrogen bond to the
malonyl thioester oxo group, and the other abstracts a proton from the leaving
group. CONCLUSIONS: The same mechanism is proposed for KAS II, which also has a
Cys-His-His active site triad. Comparison to the active site architectures of
other thiolase fold enzymes carrying out a decarboxylation step suggests that
chalcone synthase and KAS III with Cys-His-Asn triads use another mechanism in
which both the histidine and the asparagine interact with the thioester oxo
group. The acyl binding pockets of KAS I and KAS II are so similar that they
alone cannot provide the basis for their differences in substrate specificity.
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Figure 1.
Figure 1. The Three-Step Mechanism Characterizing the
Decarboxylating Claisen Condensing EnzymesThe first step is a
trans-thioesterification of the primer substrate. Subsequently,
malonyl-ACP gets decarboxylated to give the carbanion, which
then attacks C1 of the primer substrate, followed by release of
the product, 3-oxoacyl-ACP
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2001,
9,
233-243)
copyright 2001.
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