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PDBsum entry 2o1x
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References listed in PDB file
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Key reference
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Title
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Crystal structure of 1-Deoxy-D-Xylulose 5-Phosphate synthase, A crucial enzyme for isoprenoids biosynthesis.
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Authors
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S.Xiang,
G.Usunow,
G.Lange,
M.Busch,
L.Tong.
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Ref.
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J Biol Chem, 2007,
282,
2676-2682.
[DOI no: ]
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PubMed id
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Abstract
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Isopentenyl pyrophosphate (IPP) is a common precursor for the synthesis of all
isoprenoids, which have important functions in living organisms. IPP is produced
by the mevalonate pathway in archaea, fungi, and animals. In contrast, IPP is
synthesized by a mevalonate-independent pathway in most bacteria, algae, and
plant plastids. 1-Deoxy-D-xylulose 5-phosphate synthase (DXS) catalyzes the
first and the rate-limiting step of the mevalonate-independent pathway and is an
attractive target for the development of novel antibiotics, antimalarials, and
herbicides. We report here the first structural information on DXS, from
Escherichia coli and Deinococcus radiodurans, in complex with the coenzyme
thiamine pyrophosphate (TPP). The structure contains three domains (I, II, and
III), each of which bears homology to the equivalent domains in transketolase
and the E1 subunit of pyruvate dehydrogenase. However, DXS has a novel
arrangement of these domains as compared with the other enzymes, such that the
active site of DXS is located at the interface of domains I and II in the same
monomer, whereas that of transketolase is located at the interface of the dimer.
The coenzyme TPP is mostly buried in the complex, but the C-2 atom of its
thiazolium ring is exposed to a pocket that is the substrate-binding site. The
structures identify residues that may have important roles in catalysis, which
have been confirmed by our mutagenesis studies.
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Figure 3.
FIGURE 3. Crystal structures of DXS. A, schematic drawing
in stereo of the structure of the D. radiodurans DXS dimer. The
three domains of one monomer are colored cyan, green, and
yellow, respectively, and the linker between domains I and II is
colored red. The other monomer is colored gray. TPP is shown as
a stick model in magenta. The 2-fold axis of the dimer is
vertical. B, structure of E. coli DXS dimer, in the same
orientation and color scheme as A. The images were produced with
PyMol (44).
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Figure 4.
FIGURE 4. Crystal structures of transketolase and pyruvate
dehydrogenase E1 subunit. A, schematic drawing of the structure
of yeast transketolase dimer (35). B, structure of E. coli
pyruvate dehydrogenase E1 subunit dimer (36). The structures are
viewed in the same orientation as that for DXS in Fig. 3. The
images were produced with PyMol (44).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
2676-2682)
copyright 2007.
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