8IJZ

anti-VEGF mutant

Summary for 8IJZ

• Entry DOI: 10.2210/pdb8ijz/pdb
• Descriptor: anti-VEGF nanobody (1 entity in total)
• Functional Keywords: anti-vegf, nanobody, antitumor protein, antitumor protein-immune system
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 13731.32

Authors

Qian, F.,Zhu, S.Q. (deposition date: 2023-02-28, release date: 2023-12-27, Last modification date: 2024-10-09)

Primary citation

Zhu, S.,Fan, S.,Tang, T.,Huang, J.,Zhou, H.,Huang, C.,Chen, Y.,Qian, F.
Polymorphic nanobody crystals as long-acting intravitreal therapy for wet age-related macular degeneration.
Bioeng Transl Med, 8:e10523-e10523, 2023

PubMed Abstract: Wet age-related macular degeneration (wet AMD) is the most common cause of blindness, and chronic intravitreal injection of anti-vascular endothelial growth factor (VEGF) proteins has been the dominant therapeutic approach. Less intravitreal injection and a prolonged inter-injection interval are the main drivers behind new wet AMD drug innovations. By rationally engineering the surface residues of a model anti-VEGF nanobody, we obtained a series of anti-VEGF nanobodies with identical protein structures and VEGF binding affinities, while drastically different crystallization propensities and crystal lattice structures. Among these nanobody crystals, the 222 lattice appeared to be denser and released protein slower than the 1 lattice, while nanobody crystals embedding zinc coordination further slowed the protein release rate. The polymorphic protein crystals could be a potentially breakthrough strategy for chronic intravitreal administration of anti-VEGF proteins.

PubMed: 38023710
DOI: 10.1002/btm2.10523

Experimental method

ELECTRON CRYSTALLOGRAPHY (2.1 Å)