7Y0G

Crystal structure of anti-mPEG h15-2b Fab

Summary for 7Y0G

• Entry DOI: 10.2210/pdb7y0g/pdb
• Descriptor: 15-2b light chain, 15-2b heavy chain, 2,5,8,11,14,17-HEXAOXANONADECAN-19-OL, ... (4 entities in total)
• Functional Keywords: methoxy polyethylene glycol, anti-mpeg antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 8
• Total formula weight: 193735.53

Authors

Chang, C.Y.,Nguyen, T.M.T.,Lin, E.C.,Su, Y.C. (deposition date: 2022-06-05, release date: 2022-08-10, Last modification date: 2024-11-06)

Primary citation

Nguyen, M.T.,Shih, Y.C.,Lin, M.H.,Roffler, S.R.,Hsiao, C.Y.,Cheng, T.L.,Lin, W.W.,Lin, E.C.,Jong, Y.J.,Chang, C.Y.,Su, Y.C.
Structural determination of an antibody that specifically recognizes polyethylene glycol with a terminal methoxy group.
Commun Chem, 5:88-88, 2022

PubMed Abstract: Covalent attachment of methoxy poly(ethylene) glycol (mPEG) to therapeutic molecules is widely employed to improve their systemic circulation time and therapeutic efficacy. mPEG, however, can induce anti-PEG antibodies that negatively impact drug therapeutic effects. However, the underlying mechanism for specific binding of antibodies to mPEG remains unclear. Here, we determined the first co-crystal structure of the humanized 15-2b anti-mPEG antibody in complex with mPEG, which possesses a deep pocket in the antigen-binding site to accommodate the mPEG polymer. Structural and mutational analyses revealed that mPEG binds to h15-2b via Van der Waals and hydrogen bond interactions, whereas the methoxy group of mPEG is stabilized in a hydrophobic environment between the V:V interface. Replacement of the heavy chain hydrophobic V37 residue with a neutral polar serine or threonine residue offers additional hydrogen bond interactions with methoxyl and hydroxyl groups, resulting in cross-reactivity to mPEG and OH-PEG. Our findings provide insights into understanding mPEG-binding specificity and antigenicity of anti-mPEG antibodies.

PubMed: 35936993
DOI: 10.1038/s42004-022-00709-0

Experimental method

X-RAY DIFFRACTION (2.08 Å)