1S5O

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

1S5O の概要

• エントリーDOI: 10.2210/pdb1s5o/pdb
• 分子名称: carnitine acetyltransferase isoform 2, CARNITINE (3 entities in total)
• 機能のキーワード: carnitine acetyltransferase, binary complex, steady-state enzyme kinetics, substrate binding site, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum (Potential). Isoform 1: Mitochondrion (Potential). Isoform 2: Peroxisome (Potential): P43155
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 70065.07

構造登録者

Govindasamy, L.,Kukar, T.,Lian, W.,Pedersen, B.,Gu, Y.,Agbandje-Mckenna, M.,Jin, S.,Mckenna, R.,Wu, D. (登録日: 2004-01-21, 公開日: 2004-02-03, 最終更新日: 2023-08-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)