6WIB
Next generation monomeric IgG4 Fc
Summary for 6WIB
Entry DOI | 10.2210/pdb6wib/pdb |
Descriptor | Immunoglobulin heavy constant gamma 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (4 entities in total) |
Functional Keywords | antibody constant region, fragment crystallizable, mutated, immune system |
Biological source | Homo sapiens (Human) |
Total number of polymer chains | 1 |
Total formula weight | 25507.53 |
Authors | Oganesyan, V.Y.,Shan, L.,Dall'Acqua, W.,van Dyk, N. (deposition date: 2020-04-09, release date: 2021-09-15, Last modification date: 2024-11-13) |
Primary citation | Shan, L.,Dyk, N.V.,Haskins, N.,Cook, K.M.,Rosenthal, K.L.,Mazor, R.,Dragulin-Otto, S.,Jiang, Y.,Wu, H.,Dall'Acqua, W.F.,Borrok, M.J.,Damschroder, M.M.,Oganesyan, V. In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance. Commun Biol, 4:1048-1048, 2021 Cited by PubMed Abstract: In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life. PubMed: 34497355DOI: 10.1038/s42003-021-02565-5 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.55 Å) |
Structure validation
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