2C1P

Fab-fragment of enantioselective antibody complexed with finrozole

2C1P の概要

• エントリーDOI: 10.2210/pdb2c1p/pdb
• 関連するPDBエントリー: 1AFV 2C1O
• 分子名称: IGK-C PROTEIN, IGH-4 PROTEIN, 4-[(1S,2R)-3-(4-FLUOROPHENYL)-2-HYDROXY-1-(1H-1,2,4-TRIAZOL-1-YL)PROPYL]BENZONITRILE, ... (4 entities in total)
• 機能のキーワード: fab fragment, enantioselective, finrozole, immune system, antibody, enantioselective antibody, immunoglobulin domain
• 由来する生物種: MUS MUSCULUS (MOUSE); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 95432.42

構造登録者

Parkkinen, T.,Nevanen, T.K.,Koivula, A.,Rouvinen, J. (登録日: 2005-09-19, 公開日: 2006-01-25, 最終更新日: 2024-11-13)

主引用文献

Parkkinen, T.,Nevanen, T.K.,Koivula, A.,Rouvinen, J.
Crystal Structures of an Enantioselective Fab-Fragment in Free and Complex Forms.
J.Mol.Biol., 357:471-, 2006

PubMed Abstract: Enantioselective antibodies can separate the enantiomers of a chiral compound in a highly specific manner. We have recently reported the cloning and applications of a recombinant Fab-fragment, ENA11His, in the enantioseparation of a drug candidate, finrozole, which contains two chiral centers. Here, the crystal structures of this enantioselective antibody Fab-fragment are determined in the absence of the hapten at a resolution of 2.75 A, and in the presence of the hapten at 2.05 A resolution. The conformation of the protein was found to be similar in both free and complex forms. The hapten molecule was tightly bound in a deep cleft between the light and heavy chains of the Fab-fragment. The complex structure also allowed us to describe the molecular basis for enantioselectivity and to deduce the absolute configurations of all the four different stereoisomers (a-d) of finrozole. The ENA11His antibody fragment selectively binds the SR (a) enantiomer from the racemic mixture of a and d-enantiomers, thus allowing separation from the pharmacologically most active RS enantiomer (d). In particular, Asp95 and Asn35 of the H-chain in the ENA11 His antibody seem to provide this specificity through hydrogen bonding.

PubMed: 16427081
DOI: 10.1016/J.JMB.2005.12.045

実験手法

X-RAY DIFFRACTION (2 Å)