2WQ5

Non-antibiotic properties of tetracyclines: structural basis for inhibition of secretory phospholipase A2.

2WQ5 の概要

• エントリーDOI: 10.2210/pdb2wq5/pdb
• 関連するPDBエントリー: 1A3D 1A3F 1OWS 1PSH
• 分子名称: PHOSPHOLIPASE A2, ACIDIC, CALCIUM ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, minocycline, phospholipase, metal-binding, lipid degradation, calcium binding loop, carboxylic ester hydrolase
• 由来する生物種: NAJA NAJA (INDIAN COBRA)
• 細胞内の位置: Secreted : P15445
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13949.63

構造登録者

Dalm, D.,Palm, G.J.,Hinrichs, W. (登録日: 2009-08-13, 公開日: 2010-03-23, 最終更新日: 2024-11-06)

主引用文献

Dalm, D.,Palm, G.J.,Aleksandrov, A.,Simonson, T.,Hinrichs, W.
Non-Antibiotic Properties of Tetracyclines: Structural Basis for Inhibition of Secretory Phospholipase A(2).
J.Mol.Biol., 398:83-, 2010

PubMed Abstract: Secretory phospholipase A(2) is involved in inflammatory processes and was previously shown to be inhibited by lipophilic tetracyclines such as minocycline (minoTc) and doxycycline. Lipophilic tetracyclines might be a new lead compound for the design of specific inhibitors of secretory phospholipase A(2), which play a crucial role in inflammatory processes. Our X-ray crystal structure analysis at 1.65 A resolution of the minoTc complex of phospholipase A(2) (PLA(2)) of the Indian cobra (Naja naja naja) is the first example of nonantibiotic tetracycline interactions with a protein. MinoTc interferes with the conformation of the active-site Ca(2+)-binding loop, preventing Ca(2)(+) binding, and shields the active site from substrate entrance, resulting in inhibition of the enzyme. MinoTc binding to PLA(2) is dominated by hydrophobic interactions quite different from antibiotic recognition of tetracyclines by proteins or the ribosome. The affinity of minoTc for PLA(2) was determined by surface plasmon resonance, resulting in a dissociation constant K(d)=1.8 x 10(-)(4) M.

PubMed: 20211188
DOI: 10.1016/J.JMB.2010.02.049

実験手法

X-RAY DIFFRACTION (1.65 Å)