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J Biol Chem, Vol. 274, Issue 51, 36465-36471, December 17, 1999
From SmithKline Beecham Pharmaceuticals,
King of Prussia, Pennsylvania 19406
The atomic coordinates and the structure factors (code 1D9B) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
Crystal Structure of
-Ketoacyl-Acyl Carrier Protein Synthase
III
A KEY CONDENSING ENZYME IN BACTERIAL FATTY ACID
BIOSYNTHESIS*
,
-Ketoacyl-acyl carrier protein synthase III
(FabH), the most divergent member of the family of condensing enzymes,
is a key catalyst in bacterial fatty acid biosynthesis and a promising target for novel antibiotics. We report here the crystal structures of
FabH determined in the presence and absence of acetyl-CoA. These
structures display a fold that is common for condensing enzymes. The
observed acetylation of Cys112 proves its catalytic
role and clearly defines the primer binding pocket. Modeling based on a
bound CoA molecule suggests catalytic roles for His244 and
Asn274. The structures provide the molecular basis for FabH
substrate specificity and reaction mechanism and are important for
structure-based design of novel antibiotics.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 610-270-4589;
Fax: 610-270-4091; E-mail: xiayang_qiu-1@sbphrd.com.
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