1S5O

Structural and Mutational Characterization of L-carnitine Binding to Human carnitine Acetyltransferase

Summary for 1S5O

• Entry DOI: 10.2210/pdb1s5o/pdb
• Descriptor: carnitine acetyltransferase isoform 2, CARNITINE (3 entities in total)
• Functional Keywords: carnitine acetyltransferase, binary complex, steady-state enzyme kinetics, substrate binding site, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum (Potential). Isoform 1: Mitochondrion (Potential). Isoform 2: Peroxisome (Potential): P43155
• Total number of polymer chains: 1
• Total formula weight: 70065.07

Authors

Govindasamy, L.,Kukar, T.,Lian, W.,Pedersen, B.,Gu, Y.,Agbandje-Mckenna, M.,Jin, S.,Mckenna, R.,Wu, D. (deposition date: 2004-01-21, release date: 2004-02-03, Last modification date: 2023-08-23)

Primary citation

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., 146:416-424, 2004

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.

PubMed: 15099582
DOI: 10.1016/j.jsb.2004.01.011

Experimental method

X-RAY DIFFRACTION (1.8 Å)