W0176

Structure of Human Carnitine Acetyltransferase: Molecular Basis for Fatty Acyl Transfer. Robert McKenna, Govindasamy Lakshmanan, Lian Wei, Gu Yunrong, Kukar Thomas, Wu Donghai, Agbandje-McKenna Mavis, Dept. of Biochemistry and Molecular Biology, Univ. of Florida, 1600 Archer Road, Gainesville, FL 100245 USA.

Carnitine acetyltransferase is a member of fatty acyl group transfer-dependent enzyme, which catalyzes the transfer of acyl group esters between carnitine and coenzyme (CoA). Carnitine acyltransferases are a family of ubiquitous enzymes that play a pivotal role in cellular energy metabolism. This structure reveals a monomeric protein of two equally sized α/β domains. Each domain is shown to have a partially similar fold to other known, though oligomeric enzymes, which 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. 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”. The X-ray structure of human carnitine acetyltransferase and its complex with carnitine will be discussed in terms of catalytic function.