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PDBsum entry 1od4
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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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Crystal structure of the carboxyltransferase domain of acetyl-Coenzyme a carboxylase.
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Authors
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H.Zhang,
Z.Yang,
Y.Shen,
L.Tong.
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Ref.
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Science, 2003,
299,
2064-2067.
[DOI no: ]
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PubMed id
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Abstract
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Acetyl-coenzyme A carboxylases (ACCs) are required for the biosynthesis and
oxidation of long-chain fatty acids. They are targets for therapeutics against
obesity and diabetes, and several herbicides function by inhibiting their
carboxyltransferase (CT) domain. We determined the crystal structure of the free
enzyme and the coenzyme A complex of yeast CT at 2.7 angstrom resolution and
found that it comprises two domains, both belonging to the crotonase/ClpP
superfamily. The active site is at the interface of a dimer. Mutagenesis and
kinetic studies reveal the functional roles of conserved residues here. The
herbicides target the active site of CT, providing a lead for inhibitor
development against human ACCs.
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Figure 1.
Fig. 1. Structures of ACCs. (A) Schematic drawing of the
primary structures of eukaryotic multidomain ACC and bacterial
multisubunit ACC. (B) The chemical reaction catalyzed by CT. The
N1 atom of biotin is labeled. (C) Schematic drawing of the
structure of the CT domain dimer of yeast ACC. The N and C
domains of one monomer are colored cyan and yellow, whereas
those of the other monomer are colored purple and green. The CoA
molecule bound to one monomer is shown as a stick model. Only
the adenine base was observed in the other monomer (labeled A).
(C) was produced with Ribbons (22).
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Figure 3.
Fig. 3. The active site of CT and the binding mode of CoA. (A)
Schematic drawing in stereo of the active site of CT. The N
domain is shown in cyan, and the C domain of the other monomer
is shown in green. The side chains of residues in the active
site are shown in purple. The prime (') in the labels indicates
the C domain of the other monomer of the dimer. (B) Molecular
surface of the active site region of CT. The side chain of
Lys1764 (in helix  6, 15
Å from the active site) has been removed to facilitate the
viewing of the active site. (C) Chemical structure of haloxyfop
and the double reciprocal plot showing the competitive
inhibition of wild-type yeast CT by haloxyfop. (A) was produced
with Ribbons (22), and (B) with Grasp (23).
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The above figures are
reprinted
by permission from the AAAs:
Science
(2003,
299,
2064-2067)
copyright 2003.
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