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J. Biol. Chem., Vol. 278, Issue 15, 13159-13165, April 11, 2003
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From the Carnitine acyltransferases are a family of
ubiquitous enzymes that play a pivotal role in cellular energy
metabolism. We report here the x-ray structure of human carnitine
acetyltransferase to a 1.6-Å resolution. This structure reveals
a monomeric protein of two equally sized The atomic coordinates and the structure factors (code 1NM8) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
Structure of Human Carnitine Acetyltransferase
MOLECULAR BASIS FOR FATTY ACYL TRANSFER*
,
,
,
,
Department of Medicinal Chemistry, College
of Pharmacy and § Department of Biochemistry and Molecular
Biology, College of Medicine, University of Florida, Gainesville,
Florida 32610
/
domains. Each domain
is shown to have a partially similar fold to other known but oligomeric
enzymes that are also involved in group-transfer reactions. The unique monomeric arrangement of the two domains constitutes a central narrow
active site tunnel, indicating a likely universal feature for all
members of the carnitine acyltransferase family. Superimposition of the
substrate complex of a related protein, dihydrolipoyl trans-acetylase, reveals that both substrates localize to the active site tunnel of
human carnitine acetyltransferase, suggesting the location of the
ligand binding sites for carnitine and coenzyme A. Most significantly,
this structure provides critical insights into the molecular basis for
fatty acyl chain transfer and a possible common mechanism among a wide
range of acyltransferases utilizing a catalytic dyad.
*
This work was supported in part by the University of
Florida, College of Medicine start-up funds (to R. M.) and National
Institutes of Health Grant R01 GM58197 (to D. H. W.).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.
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