3LS4

Crystal Structure of Anti-tetrahydrocannabinol Fab Fragment in Complex with THC

3LS4 の概要

• エントリーDOI: 10.2210/pdb3ls4/pdb
• 関連するPDBエントリー: 3LS5
• 分子名称: Light chain of antibody Fab fragment, Heavy chain of antibody Fab fragment, (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol, ... (4 entities in total)
• 機能のキーワード: immune system, antibody, immunoglobulin, fab fragment, cannabinoid complex
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47032.73

構造登録者

Niemi, M.H.,Rouvinen, J. (登録日: 2010-02-12, 公開日: 2010-06-02, 最終更新日: 2024-11-20)

主引用文献

Niemi, M.H.,Turunen, L.,Pulli, T.,Nevanen, T.K.,Hoyhtya, M.,Soderlund, H.,Rouvinen, J.,Takkinen, K.
A structural insight into the molecular recognition of a (-)-Delta9-tetrahydrocannabinol and the development of a sensitive, one-step, homogeneous immunocomplex-based assay for its detection
J.Mol.Biol., 400:803-814, 2010

PubMed Abstract: (-)-Delta9-tetrahydrocannabinol (THC) is the main psychoactive compound found in cannabis. In this study, an anti-THC Fab fragment, designed T3, was isolated from a display library cloned from the spleen cells of a mouse immunized with a THC-bovine serum albumin conjugate, and the crystal structures of the T3 Fab in its free form and in complex with THC were determined at 1.9 A and 2.0 A resolution, respectively. The THC binding site of the T3 Fab is a narrow cavity: the n-pentyl group of THC protrudes deep into the interface area between the variable domains and the C(10) monoterpene moiety of the hapten is partially exposed to solvent. The metabolites of THC, with modifications in the C(10) monoterpene moiety, 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol and 11-hydroxy-?(9)-tetrahydrocannabinol, are bound by the T3 Fab with a higher affinity than THC. The crystal structures suggest that Ser52H and Arg53H of the T3 Fab are able to make hydrogen bonds with the metabolites, which leads to an increased binding against these metabolites. By developing a T3 Fab-Delta(9)-THC immunocomplex binding antibody from a naïve antibody phage display library, the specificity of the Delta(9)-THC binding is highly increased, which allows a one-step, homogeneous, fluorescence resonance energy transfer-based sensitive immunoassay, with a detection limit of 20 ng/ml from saliva samples.

PubMed: 20630472
DOI: 10.1016/j.jmb.2010.05.048

実験手法

X-RAY DIFFRACTION (2 Å)