7U63

Crystal Structure Anti-Oxycodone Antibody HY2-A12 Fab Complexed with Oxycodone

7U63 の概要

• エントリーDOI: 10.2210/pdb7u63/pdb
• 分子名称: HY2-A12 Fab Light Chain, HY2-A12 Fab Heavy Chain, 14-hydroxy-3-methoxy-17-methyl-5beta-4,5-epoxymorphinan-6-one, ... (4 entities in total)
• 機能のキーワード: mab, opioid, immune system
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 142036.56

構造登録者

Rodarte, J.V.,Pancera, M.P.,Weidle, C.,Rupert, P.B.,Strong, R.K. (登録日: 2022-03-03, 公開日: 2023-01-11, 最終更新日: 2024-11-06)

主引用文献

Rodarte, J.V.,Baehr, C.,Hicks, D.,Liban, T.L.,Weidle, C.,Rupert, P.B.,Jahan, R.,Wall, A.,McGuire, A.T.,Strong, R.K.,Runyon, S.,Pravetoni, M.,Pancera, M.
Structures of drug-specific monoclonal antibodies bound to opioids and nicotine reveal a common mode of binding.
Structure, 31:20-32.e5, 2023

PubMed Abstract: Opioid-related fatal overdoses have reached epidemic proportions. Because existing treatments for opioid use disorders offer limited long-term protection, accelerating the development of newer approaches is critical. Monoclonal antibodies (mAbs) are an emerging treatment strategy that targets and sequesters selected opioids in the bloodstream, reducing drug distribution across the blood-brain barrier, thus preventing or reversing opioid toxicity. We previously identified a series of murine mAbs with high affinity and selectivity for oxycodone, morphine, fentanyl, and nicotine. To determine their binding mechanism, we used X-ray crystallography to solve the structures of mAbs bound to their respective targets, to 2.2 Å resolution or higher. Structural analysis showed a critical convergent hydrogen bonding mode that is dependent on a glutamic acid residue in the mAbs' heavy chain and a tertiary amine of the ligand. Characterizing drug-mAb complexes represents a significant step toward rational antibody engineering and future manufacturing activities to support clinical evaluation.

PubMed: 36513069
DOI: 10.1016/j.str.2022.11.008

実験手法

X-RAY DIFFRACTION (2.3 Å)