2ZWS

Crystal Structure Analysis of neutral ceramidase from Pseudomonas aeruginosa

2ZWS の概要

• エントリーDOI: 10.2210/pdb2zws/pdb
• 分子名称: Neutral ceramidase, ZINC ION, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: prism fold and beta-sandwich fold, hydrolase, lipid metabolism, secreted
• 由来する生物種: Pseudomonas aeruginosa
• 細胞内の位置: Secreted (Potential): Q9I596
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 72905.08

構造登録者

Kakuta, Y.,Okino, N.,Inoue, T.,Okano, H.,Ito, M. (登録日: 2008-12-17, 公開日: 2009-03-03, 最終更新日: 2024-10-23)

主引用文献

Inoue, T.,Okino, N.,Kakuta, Y.,Hijikata, A.,Okano, H.,Goda, H.M.,Tani, M.,Sueyoshi, N.,Kambayashi, K.,Matsumura, H.,Kai, Y.,Ito, M.
Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral ceramidase.
J.Biol.Chem., 284:9566-9577, 2009

PubMed Abstract: Ceramidase (CDase; EC 3.5.1.23) hydrolyzes ceramide to generate sphingosine and fatty acid. The enzyme plays a regulatory role in a variety of physiological events in eukaryotes and also functions as an exotoxin in particular bacteria. The crystal structures of neutral CDase from Pseudomonas aeruginosa (PaCD) in the C2-ceramide-bound and -unbound forms were determined at 2.2 and 1.4 A resolutions, respectively. PaCD consists of two domains, and the Zn(2+)- and Mg(2+)/Ca(2+)-binding sites are found within the center of the N-terminal domain and the interface between the domains, respectively. The structural comparison between the C2-ceramide-bound and unbound forms revealed an open-closed conformational change occurring to loop I upon binding of C2-ceramide. In the closed state, this loop sits above the Zn(2+) coordination site and over the opening to the substrate binding site. Mutational analyses of residues surrounding the Zn(2+) of PaCD and rat neutral CDase revealed that the cleavage or creation of the N-acyl linkage of ceramide follows a similar mechanism as observed for the Zn(2+)-dependent carboxypeptidases. The results provide an understanding of the molecular mechanism of hydrolysis and synthesis of ceramide by the enzyme. Furthermore, insights into the actions of PaCD and eukaryotic neutral CDases as an exotoxin and mediators of sphingolipid signaling are also revealed, respectively.

PubMed: 19088069
DOI: 10.1074/jbc.M808232200

実験手法

X-RAY DIFFRACTION (1.4 Å)