6BI0

Trastuzumab Fab N158A, D185A, K190A (Light Chain) Triple Mutant.

6BI0 の概要

• エントリーDOI: 10.2210/pdb6bi0/pdb
• 関連するPDBエントリー: 6BHZ
• 分子名称: Trastuzumab anti-HER2 Fab Heavy Chain, Trastuzumab anti-HER2 Fab Light Chain, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: fab, immunoglobulin, mutant, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94991.90

構造登録者

DiDonato, M.,Spraggon, G. (登録日: 2017-10-31, 公開日: 2018-02-14, 最終更新日: 2024-11-13)

主引用文献

Pham, G.H.,Ou, W.,Bursulaya, B.,DiDonato, M.,Herath, A.,Jin, Y.,Hao, X.,Loren, J.,Spraggon, G.,Brock, A.,Uno, T.,Geierstanger, B.H.,Cellitti, S.E.
Tuning a Protein-Labeling Reaction to Achieve Highly Site Selective Lysine Conjugation.
Chembiochem, 19:799-804, 2018

PubMed Abstract: Activated esters are widely used to label proteins at lysine side chains and N termini. These reagents are useful for labeling virtually any protein, but robust reactivity toward primary amines generally precludes site-selective modification. In a unique case, fluorophenyl esters are shown to preferentially label human kappa antibodies at a single lysine (Lys188) within the light-chain constant domain. Neighboring residues His189 and Asp151 contribute to the accelerated rate of labeling at Lys188 relative to the ≈40 other lysine sites. Enriched Lys188 labeling can be enhanced from 50-70 % to >95 % by any of these approaches: lowering reaction temperature, applying flow chemistry, or mutagenesis of specific residues in the surrounding protein environment. Our results demonstrated that activated esters with fluoro-substituted aromatic leaving groups, including a fluoronaphthyl ester, can be generally useful reagents for site-selective lysine labeling of antibodies and other immunoglobulin-type proteins.

PubMed: 29388367
DOI: 10.1002/cbic.201700611

実験手法

X-RAY DIFFRACTION (2.057 Å)