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PDBsum entry 1f7l
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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 structures of substrate binding to bacillus subtilis holo-(Acyl carrier protein) synthase reveal a novel trimeric arrangement of molecules resulting in three active sites.
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Authors
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K.D.Parris,
L.Lin,
A.Tam,
R.Mathew,
J.Hixon,
M.Stahl,
C.C.Fritz,
J.Seehra,
W.S.Somers.
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Ref.
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Structure, 2000,
8,
883-895.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Holo-(acyl carrier protein) synthase (AcpS), a member of the
phosphopantetheinyl transferase superfamily, plays a crucial role in the
functional activation of acyl carrier protein (ACP) in the fatty acid
biosynthesis pathway. AcpS catalyzes the attachment of the
4'-phosphopantetheinyl moiety of coenzyme A (CoA) to the sidechain of a
conserved serine residue on apo-ACP. RESULTS: We describe here the first crystal
structure of a type II ACP from Bacillus subtilis in complex with its activator
AcpS at 2.3 A. We also have determined the structures of AcpS alone (at 1.8 A)
and AcpS in complex with CoA (at 1.5 A). These structures reveal that AcpS
exists as a trimer. A catalytic center is located at each of the solvent-exposed
interfaces between AcpS molecules. Site-directed mutagenesis studies confirm the
importance of trimer formation in AcpS activity. CONCLUSIONS: The active site in
AcpS is only formed when two AcpS molecules dimerize. The addition of a third
molecule allows for the formation of two additional active sites and also
permits a large hydrophobic surface from each molecule of AcpS to be buried in
the trimer. The mutations Ile5-->Arg, Gln113-->Glu and Gln113-->Arg show that
AcpS is inactive when unable to form a trimer. The co-crystal structures of
AcpS-CoA and AcpS-ACP allow us to propose a catalytic mechanism for this class
of 4'-phosphopantetheinyl transferases.
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Figure 6.
Figure 6. The mechanism that can be derived from the
crystal structures in this study. The metal-bound water molecule
removes the hydrogen from Ser36, converting it into a
nucleophile and thereby initiating P-pant transfer and
activation of ACP.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
883-895)
copyright 2000.
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