Structural and mutational characterization of L-carnitine binding to human carnitine acetyltransferase.

Article Details

Citation

Copy to clipboard

Govindasamy L, Kukar T, Lian W, Pedersen B, Gu Y, Agbandje-McKenna M, Jin S, McKenna R, Wu D

Structural and mutational characterization of L-carnitine binding to human carnitine acetyltransferase.

J Struct Biol. 2004 Jun;146(3):416-24.

PubMed ID

15099582 [ View in PubMed

]

Abstract

We report the crystal structure of a binary complex of human peroxisomal carnitine acetyltransferase and the substrate l-carnitine, refined to a resolution of 1.8 Angstrom with an R(factor) value of 18.9% (R(free)=22.3%). L-carnitine binds to a preformed pocket in the active site tunnel of carnitine acetyltransferase aligned with His(322). The quaternary nitrogen of carnitine forms a pi-cation interaction with Phe(545), while Arg(497) forms an electrostatic interaction with the negatively charged carboxylate group. An extensive hydrogen bond network also occurs between the carboxylate group and Tyr(431), Thr(444), and a bound water molecule. Site-directed mutagenesis and kinetic characterization reveals that Tyr(431), Thr(444), Arg(497), and Phe(545) are essential for high affinity binding of L-carnitine.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Levocarnitine	Carnitine O-acetyltransferase	Protein	Humans	Unknown	Not Available	Details

Polypeptides

Name	UniProt ID
Carnitine O-acetyltransferase	P43155	Details