5T1K

Cetuximab Fab in complex with CQFDA(Ph)2STRRLKC

5T1K の概要

• エントリーDOI: 10.2210/pdb5t1k/pdb
• 関連するPDBエントリー: 4GW1 4IWE 5ETU 5EUK 5F88 5FF6 5I2I 5IOP 5IR1 5ITF 5IV2 5IVZ 5T1L 5T1M 5TH2
• 分子名称: CETUXIMAB FAB LIGHT CHAIN, CETUXIMAB FAB HEAVY CHAIN, CQFDA(PH)2STRRLKC PEPTIDE, ... (7 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, Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 97772.10

構造登録者

Bzymek, K.P.,Williams, J.C. (登録日: 2016-08-19, 公開日: 2016-10-26, 最終更新日: 2023-11-15)

主引用文献

Bzymek, K.P.,Avery, K.A.,Ma, Y.,Horne, D.A.,Williams, J.C.
Natural and non-natural amino-acid side-chain substitutions: affinity and diffraction studies of meditope-Fab complexes.
Acta Crystallogr F Struct Biol Commun, 72:820-830, 2016

PubMed Abstract: Herein, multiple crystal structures of meditope peptide derivatives incorporating natural and unnatural amino acids bound to the cetuximab Fab domain are presented. The affinity of each derivative was determined by surface plasmon resonance and correlated to the atomic structure. Overall, it was observed that the hydrophobic residues in the meditope peptide, Phe3, Leu5 and Leu10, could accommodate a number of moderate substitutions, but these invariably reduced the overall affinity and half-life of the interaction. In one case, the substitution of Phe3 by histidine led to a change in the rotamer conformation, in which the imidazole ring flipped to a solvent-exposed position. Based on this observation, Phe3 was substituted by diphenylalanine and it was found that the phenyl rings in this variant mimic the superposition of the Phe3 and His3 structures, producing a moderate increase, of 1.4-fold, in the half-life of the complex. In addition, it was observed that substitution of Leu5 by tyrosine and glutamate strongly reduced the affinity, whereas the substitution of Leu5 by diphenylalanine moderately reduced the half-life (by approximately fivefold). Finally, it was observed that substitution of Arg8 and Arg9 by citrulline dramatically reduced the overall affinity, presumably owing to lost electrostatic interactions. Taken together, these studies provide insight into the meditope-cetuximab interaction at the atomic level.

PubMed: 27834791
DOI: 10.1107/S2053230X16016149

実験手法

X-RAY DIFFRACTION (2.48 Å)