6AZL

Structure of cetuximab with aminoheptanoic acid-linked N-carboxyethylarginine meditope variant

6AZL の概要

• エントリーDOI: 10.2210/pdb6azl/pdb
• 関連するPDBエントリー: 5id0 6au5
• 分子名称: cetuximab Fab light chain, cetuximab Fab heavy chain, meditope, ... (5 entities in total)
• 機能のキーワード: antibody, anti-egfr, immune system
• 由来する生物種: Mus musculus; 詳細
• 細胞内の位置: Secreted : P01834
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 97244.03

構造登録者

Bzymek, K.P.,Williams, J.C. (登録日: 2017-09-11, 公開日: 2017-12-13, 最終更新日: 2023-11-15)

主引用文献

Bzymek, K.P.,Ma, Y.,Avery, K.N.,Horne, D.A.,Williams, J.C.
Meditope-Fab interaction: threading the hole.
Acta Crystallogr F Struct Biol Commun, 73:688-694, 2017

PubMed Abstract: Meditope, a cyclic 12-residue peptide, binds to a unique binding side between the light and heavy chains of the cetuximab Fab. In an effort to improve the affinity of the interaction, it was sought to extend the side chain of Arg8 in the meditope, a residue that is accessible from the other side of the meditope binding site, in order to increase the number of interactions. These modifications included an n-butyl and n-octyl extension as well as hydroxyl, amine and carboxyl substitutions. The atomic structures of the complexes and the binding kinetics for each modified meditope indicated that each extension threaded through the Fab `hole' and that the carboxyethylarginine substitution makes a favorable interaction with the Fab, increasing the half-life of the complex by threefold compared with the unmodified meditope. Taken together, these studies provide a basis for the design of additional modifications to enhance the overall affinity of this unique interaction.

PubMed: 29199990
DOI: 10.1107/S2053230X17016272

実験手法

X-RAY DIFFRACTION (2.482 Å)